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SYPHILIS 


BY 

LOYD  THOMPSON,  Ph.B.,  M.D. 

PHYSICIAN     TO     THE      SYPHILIS     CLINIC,      GOVERNMENT     FHEE      BATH     HOUSE;      VISITING 

UROLOGIST   TO    ST.    JOSEPH'S    HOSPITAL;     CONSULTING    PATHOLOGIST   TO    THE    LEO 

N.  LEVY  MEMORIAL  HOSPITAL,  HOT  SPRINGS,  ARKANSAS;   FIRST  LIEUTENANT, 

MEDICAL  RESERVE   CORPS,   UNITED    STATES  ARMY;    MEMBER  OF  THE 

AMERICAN     UROLOGICAL     ASSOCIATION,    AND     OF     THE 

AMERICAN    ASSOCIATION    OF    IMMUNOLOGISTS 


ILLUSTRATED   WITH    77    ENGRAVINGS  AND   7   PLATES 


LEA   &   FEBIGEE 

PHILADELPHIA    AND    NEW    YORK 
1916 


Yt. 


Entered  according  to  the  Act  of  Congress,  in  the  year  1916,  by 

LEA   &  FEBIGER, 
in  the  Office  of  the  Librarian  of  Congress.     All  rights  reserved. 


1^  C  a  0  \ 


TO 

THE    MEMORY 
OF 

HIS    FATHER 

THIS    VOLUME    IS    LOVINGLY    DEDICATED 

BY 

THE  AUTHOR 


PREFACE. 


The  advance  made  in  our  knowledge  of  syphilis  during  the  last 
fifteen  years  finds  no  equal  in  the  entire  history  of  medicine.  It 
may  well  be  maintained  that  since  the  epoch-making  work  of 
MetchnikofJ  and  Roux  in  transmitting  syphilis  to  lower  animals 
more  information  has  been  gained  concerning  this  disease  than 
was  acquired  during  all  the  preceding  centuries. 

In  preparing  this  volume  for  the  profession  it  has  been  the  aim 
of  the  author  to  present  the  subject  of  syphilis  in  as  practical  a 
manner  as  possible.  For  this  reason  a  considerable  portion  of  the 
work  is  devoted  to  diagnosis  and  treatment.  The  chapter  on 
laboratory  diagnosis  is  made  especially  full,  as  today  the  desir- 
ability, in  fact  the  necessity,  of  laboratory  aid  is  more  evident  for 
the  successful  treatment  of  syphilis  than  for  any  other  disease. 
Matters  of  theoretical  and  historical  interest,  of  course,  are  dis- 
cussed, but  usually  only  when  they  have  some  bearing  upon  the 
practical  handling  of  the  subject. 

Syphilis,  today,  no  longer  is  to  be  considered  a  genito-urinary 
disease,  nor  a  dermatological  disease,  nor  a  disease  belonging  ex- 
clusively to  any  specialty;  but  is  to  be  thought  of  as  a  disease 
requiring  knowledge  in  all  fields  of  medicine.  As  Osier  so  aptly 
remarks,  "Know  syphilis  in  all  its  manifestations  and  relations 
and  all  other  things  clinical  will  be  added  unto  you."  It  is,  however, 
the  genito-urinary  specialist  upon  whom  the  burden  of  responsibility 
should  rest,  for  he  it  is  who,  as  a  rule,  sees  syphilis  in  the  beginning, 
and  if  his  work  is  well  done  there  should  be  no  need  for  that  of 
others  in  the  majority  of  cases. 

The  author  has  drawn  freely  from  the  literature  of  syphilis  at  his 
command  for  his  material  and  has  added  his  personal  views  and 
experiences.  In  all  instances  where  possible  he  has  given  credit 
to  those  authors  whose  work  he  has  cited. 


vi  PREFACE 

The  illustrations  are,  to  a  large  extent,  from  photographs  taken 
by  the  author  of  cases  in  his  own  practice.  A  few  were  taken  by  him 
of  cases  in  the  practices  of  Doctors  E.  H.  Martin,  Charles  Dake, 
J.  B.  Shelmire,  and  at  the  Leo  N.  Levy  Memorial  Hospital  in  the 
services  of  Doctors  William  H.  Deaderick  and  M.  F.  Lautman. 
A  number  of  photographs  have  been  furnished  by  Doctors  Howard 
Fox,  Martin  F.  Engman,  Isadore  Dyer,  and  J.  B.  Shelmire.  Illus- 
trations from  other  works  also  have  been  used.  The  author  here 
wishes  to  thank  the  above-mentioned  physicians  for  the  courtesies 
extended. 

He  also  wishes  to  express  his  obligations  to  Doctor  J.  L.  Greene 
for  the  use  of  his  extensive  library  and  for  valuable  suggestions. 

The  author's  most  sincere  gratitude  is  due  to  Doctor  William  H. 
Deaderick,  who  read  the  entire  manuscript  in  the  making  and  gave 
freely  of  his  store  of  knowledge  of  the  subject  of  syphilis  as  well 
as  of  his  technical  knowledge  of  the  writer's  art. 

To  his  wife  is  due  the  author's  gratitude  for  assistance  in  con- 
sulting and  indexing  the  literature  and  for  ready  encouragement  and 
stimulation  from  the  inception  of  the  work  to  its  completion,  without 
which  it  would  have  been  impossible. 

And,  finally,  to  the  publishers,  Messrs.  Lea  &  Febiger,  the  author 
wishes  to  express  his  appreciation  for  assistance  in  selecting  the 
photographs  for  the  illustrations  and  for  unfailing  courtesy  and 
personal  encouragement  throughout  the  entire  time  from  the  first 
correspondence  concerning  the  work  to  its  completion. 

L.  T. 

Hot  Springs,  Arkansas,  1916. 


CONTENTS. 


PART  I. 


CHAPTER  I. 


History  of  Syphilis. 

Syphilis  in  the  Old  World 17 

New  World  Origin 21 

Nomenclature        .      .      .      .  ' 22 


CHAPTER  II. 

Importance  of  Syphilis. 

Geographical  Distribution 25 

Prevalence  of  Syphilis 25 

Economic  Importance 27 


CHAPTER  III. 

Etiology. 

Early  Views 30 

Microbiology 31 

Cytoryctes  Luis -. 32 

Treponema  Pallidum 32 

Morphology 33 

Location :      .      .      .      .  34 

Animal  Inoculation 34 

Agglutination 37 

Cultivation    ....'..■. .  37 

Modes  of  Transmission 40 

Direct  Contact 40 

Intermediate  Contact 41 

Secondary  Etiological  Factors 42 

Idiosyncrasy — Immunity 42 

CoUes'  Law 42 

Age 43 

Sex 43 


viii  CONTENTS 

Secondary  Etiological  Factors — 

Race 44 

Climate 45 

Occupation 45 

Civil  State 45 

Social  Condition 45 


CHAPTER  IV. 

Pathology. 

Chancre 47 

Lymphatic  Glands 48 

Cutaneous  Lesions 48 

Macular  Syphiloderm 50 

Papular  Syphiloderm 50 

Vesicular  Syphiloderm 52 

Bullous  Syphiloderm 53 

Pustular  Syphiloderm 53 

Nodular  Syphiloderm     ....'■".. 53 

Gummatous  Syphiloderm 53 

Mucous  Membranes 54 


CHAPTER  V. 

Clinical  History. 

Ricord's  Stages 55 

Ricord's  Classification  Inadequate 55 

Development  and  Course 56 

Chancre 58 

Development 58 

Location 59 

Varieties 65 

Complications 65 

Lymphatic  Glands 66 

Cutaneous  Lesions 68 

Macular  Syphiloderm    . 68 

Papular  Syphiloderm 72 

Vesicular  Syphiloderm 82 

Bullous  Syphiloderm 83 

Pustular  Syphiloderm 83 

Nodular  Syphiloderm 90 

Gummatous  Sj^philoderm 92 

Syphilis  of  the  Appendages  of  the  Skin .  95 

Hair 95 

Nails 98 


CONTENTS  IX 

Mucous  Membranes 100 

Macular  Syphilomycoderm 100 

Papular  Syphilomycoderm 101 

Gummatous  Syphilomycoderm 103 

General  Symptoms 103 

Malaise 103 

Anorexia 103 

Temperature 104 

Pulse 104 

Respiration    .      .      .    ' 104 

Polydipsia 104 

Blood-pressure 104 

Blood 104 


CHAPTEP.  VI. 

Clinical  Diagnosis. 

Chancre 108 

Lymphatic  Glands Ill 

Cutaneous  Lesions 112 

Syphilis  of  the  Appendages  of  the  Skin 118 

Mucous  Membranes 119 

General  Symptoms 121 


CHAPTER  VII. 

Laboratory  Diagnosis. 

Demonstration  of  Treponema  Pallidum 122 

Collection  of  Material 122 

Dark-field  Illumination 123 

India-ink  Method 126 

Collargol 126 

Staining  of  Smears  126 

Staining  Sections  of  Tissue .      .  127 

Paretic  Brain  Tissue 129 

Complement-fixation  Tests 130 

Principles 130 

Technic — Preparation  of  Reagents 134 

Performing  Test — Wassermann's  Method 146 

Noguchi's  Method 147 

The  Author's  Method 149 

Theory  of  Complement-fixation  in  Syphilis 154 

Value  of  Complement-fixation  Tests  in  Syphilis 155 

Provocative  Wassermann  Test 157 

Wassermann  Reaction  in  Diseases  other  than  Syphilis        ....  157 

The  Hecht- Weinberg  Reaction 158 


X  CONTENTS 

Other  Serological  Tests 159 

Cobra  Venom  Test  of  Weil 159 

Precipitin  Tests .  159 

Enzyme  Test 160 

Landau's  Color  Test .      .  160 

Luetin  Reaction 160 

Preparation 160 

Experimentation       . 161 

Mode  of  Application 161 

Reaction 161 

Value  of  Luetin  Reaction 163 

Cerebrospinal  Fluid .     ' 164 

Anatomy 164 

Physiology 164 

Physical  and  Clinical  Properties 164 

Rachicentesis 165 

Methods  of  Examination 168 

Estimation  of  Protein 168 

Lange  CoUoidal  Gold  Test 169 

Cytology 174 

Reduction  of  Fehling's  Solution 175 

Complement-fixation         175 


CHAPTER  VIII. 

Prognosis. 

The  Wassermann  Reaction  in  Prognosis 177 

Chancre 177 

Lymphatic  Glands 178 

Skin  Lesions 178 

Syphilis  of  the  Appendages  of  the  Skin 179 

Mucous  Membranes ' 180 

General  Symptoms 180 

Blood 180 

Syphilis  and  Marriage .      .  180 

Mortality 182 


CHAPTER  IX. 

Prophylaxis. 

Personal  Measures 184 

Public  Measures    .... 185 

Regulation  of  Prostitution 185 

Education 186 

Legislation  187 


CONTENTS  XI 


CHAPTER  X. 


Treatment. 

General  Treatment 188 

Hygienic •      •  188 

Dietetic 189 

Hydro  therapeutic 189 

Specific  Treatment     .      .  , 194 

Mercury  .      .      .    - 194 

Methods  of  Administration     ....            194 

Precautions  in  Administering 206 

Contraindications ....  206 

Physiological  Action 207 

Untoward  Effects .....  208 

Comparative  Value  of  Methods  of  Administering 210 

Arsenic 211 

Atoxyl 212 

Soamin 213 

Sodium  Cacodylate 213 

Venarsen 214 

Salvarsan 215 

History 215 

Physical  and  Chemical  Properties   .            .      .      .      .            .  217 

Methods  of  Administration 218 

Neosalvarsan ■ 222 

Physical  and  Chemical  Properties       .      ...      .            .  222 

Salvarsan  Natrium 223 

Dose      .      .      .      .   ' 224 

Technic  of  Injection 224 

Administration  by  Enteroclysis 229 

Advantages  of  Various  Methods  of  Injection 230 

Indications 230 

Contraindications  .231 

Preparation  of  Patient 232 

After-care  of  Patient 232 

Action  of  Salvarsan 232 

Untoward  Effects 232 

Salvarsan  Natalities 238 

The  Fate  of  Salvarsan  in  the  Body 239 

Comparative  Value  of  Mercury  and  Salvarsan     .      .      . 240 

lodin 246 

Methods  of  Administering  lodin 247 

Therapeutic  Effects 249 

Untoward  Effects 250 

Elimination  of  lodin .  251 

Symptomatic  and  Special  Treatment 252 

Chancre 252 

Lymphatic  Glands 253 


Xll 


CONTENTS 


Symptomatic  and  Special  Treatment — 

Cutaneous  Lesions 254 

Syphilis  of  the  Appendages  of  the  Slvin    .  .  255 

Mucous  Membranes 255 

The  Cure  of  Syphilis 255 


PART  II. 


Syphilis 
Heart    .... 

Pathology 

Clinical  History 

Diagnosis 

Prognosis 

Treatment 
Arteries  and  Veins 

Pathology 

Clinical  History 

Diagnosis 

Prognosis 

Treatment 


CHAPTER  XI. 

OF  THE  Circulatory  System. 


257 
257 
,258 
259 
259 
259 
2^0 
260 
261 
262 
262 
262 


CHAPTER  XII. 

Syphilis  of  the  Respiratory  Tract. 

Larynx 263 

Pathology 263 

Clinical  History  . 263 

Diagnosis 263 

Prognosis 264 

Treatment 264 

Trachea  and  Bronchi 264 

Pathology 264 

Clinical  History 264 

Diagnosis 265 

Prognosis 265 

Treatment 265 

Lungs 265 

Pathology 265 

Clinical  History 266 

Diagnosis 267 

Prognosis 267 

Treatment 267 

Pleurae 267 


CONTENTS  xiii 


CHAPTER  XIII. 

Syphilis  of  the  G astro-intestinal  Tract. 

The  Mouth  and  Pharynx 268 

Pathology 268 

Clinical  History 268 

Diagnosis 268 

Prognosis        .      .      .  , 268 

Treatment 269 

The  Esophagus 269 

Pathology 269 

Clinical  History 269 

Diagnosis 269 

Prognosis 270 

Treatment .270 

The  Stomach  and  Intestines 270 

Pathology 270 

Clinical  History 271 

Diagnosis 271 

Prognosis 272 

Treatment .  272 


CHAPTER  XIV. 

Syphilis  of  the  Liver,  Gall-bladder,  Spleen,  and  Pancreas. 

The  Liver 274 

Pathology 274 

Clinical  History 274 

Diagnosis 276 

Prognosis 276 

Treatment 277 

The  Gall-bladder 277 

The  Spleen 277 

Pathology 277 

Clinical  History 277 

Diagnosis 278 

Prognosis 278 

Treatment 278 

The  Pancreas 278 

Pathology 278 

Clinical  History 278 

Diagnosis 278 

Prognosis •.  278 

Treatment 278 


xiv  CONTENTS 


CHAPTER  XV. 


Syphilis  of  the  Breast,  Thyroid,  Thymus,  Adrenals,  and 
Pituitary  Body. 

The  Breast 279 

Pathology 279 

Chnical  History 279 

Diagnosis 279 

Prognosis 279 

Treatment 279 

The  Thyroid  Gland 280 

Pathology 280 

Clinical  History ■      •  280 

Diagnosis 280 

Prognosis 280 

Treatment 280 

The  Thymus  Gland 280 

The  Adrenals 281 

The  Pituitary  Body  .......' 281 


CHAPTER  XVI. 

Syphilis  of  the  Genito-urinary  Organs. 

The  Penis 282 

The  Testicle 282 

Pathology ...  282 

Clinical  History  .            283 

Diagnosis ...  283 

Prognosis ■ 284 

Treatment 284 

The  Prostate 284 

Pathology 284 

Clinical  History 284 

Diagnosis 284 

Prognosis 284 

Treatment 284 

The  Seminal  Vesicles 285 

The  Vagina 285 

The  Cervix 285 

Diagnosis 286 

Treatment 287 

The  Uterus 287 

The  Fallopian  Tubes .  288 

The  Ovaries 288 

The  Urethra    . 289 

Treatment .289 


CONTENTS  XV 

The  Bladder 290 

Diagnosis 290 

Prognosis        . 290 

Treatment .  290 

The  Ureter 290 

The  Kidney 291 

Pathology 291 

Clinical  History 291 

Diagnosis 292 

Prognosis 293 

Treatment 293 

CHAPTER  XVII. 

Syphilis  of  the  Bones,  Joints,  Bxjrs.e,  Tendons,  and  Muscles. 

The  Bones .294 

Pathology 294 

Clinical  History ■    .      .  295 

Diagnosis 301 

Prognosis 302 

Treatment 302 

The  Joints .  303 

Pathology 303 

Clinical  History .  305 

Diagnosis 307 

Prognosis 308 

Treatment v 308 

The  Bursa} 309 

The  Tendons , 309 

The  Muscles 310 

Prognosis 311 

Treatment 311 

CHAPTER  XVIII. 

Syphilis  of  the  Nervous  System. 

History 312 

Pathology 312 

Meninges 313 

Arteries 31^^ 

Brain  Substance 314 

Cord  Substance ' 315 

Nerves 317 

Clinical  History 317 

Meninges 317 

Arteries 322 

Brain  »Substance 323 

Cord  Substance 328 

Nerves      .      .      .      .      : 334 


XVI  CONTENTS 

Diagnosis 335 

Meninges .•      .  335 

Arteries 335 

Brain  Substance 336 

Cord  Substance 337 

Nerves .338 

Prognosis 338 

Meninges 338 

Arteries 338 

Brain  Substance 339 

Cord  Substance  ......' 339 

Nerves 340 

Mortality 340 

Treatment 341 

Standard  Treatment 354 


CHAPTER  XIX. 

Syphilis  of  the  Eye  and  Ear. 

The  Eye 356 

Pathology 356 

Clinical  History 358 

Diagnosis 361 

Prognosis 362 

Treatment 363 

The  Ear 364 

Pathology 364 

Clinical  History 365 

Diagnosis 365 

Prognosis 366 

Treatment 366 


PART  III. 


CHAPTER  XX. 

Congenital  Syphilis. 

Nomenclature 367 

Historical 367 

Etiology 368 

Secondary  Etiological  Factors 370 

Syphilis  in  the  Third  Generation 371 


CONTENTS  xvii 


CHAPTER  XXI. 

General  Pathology  and  Clinical  History. 

Placenta 372 

Lymphatic  Glands 374 

Cutaneous  Lesions 374 

Macular  Syphiloderm 374 

Papular  Syphiloderm 375 

Maculopapular  Syphiloderm 375 

Vesicular  Syphiloderm 375 

Bullous  Syphiloderm 376 

Pustular  Syphiloderm 376 

Nodular  Syphiloderm     . 378 

Gummatous  Syphiloderm •     .  378 

Syphilis  of  the  Appendages  of  the  Skin 379 

Mucous  Membranes 379 

General  Symptoms 379 

Temperature 379 

Blood        379. 

CHAPTER  XXII. 

Regional  Syphilis. 

Syphilis  of  the  Circulatory  System 381 

Heart 381 

Arteries 382 

Veins 382 

Syphilis  of  the  Respiratory  Tract 382 

Rhinitis 382 

Larynx 382 

Trachea  and  Bronchi 383 

Lungs 383 

Syphilis  of  the  Gastro-intestinal  Tract 383 

Mouth 383 

Teeth 383 

Esophagus,  Stomach,  and  Intestines 384 

Liver 385 

Gall-bladder 386 

Spleen 386 

Pancreas 386 

The  Thyroid  Gland 386 

The  Thymus  Gland 386 

The  Adrenals 387 

The  Genito-urinary  Organs .  387 

Testicles •.  387 

Uterus  and  Ovaries 387 

Kidney  " 387 


xviii  CONTENTS 

The  Bones 388 

The  Joints 390 

The  Bursse 390 

The  Tendons  and  Muscles .391 

The  Nervous  System 392 

The  Eye     . 396 

The  Ear 397 


CHAPTER  XXIII. 

Diagnosis. 

Laboratory  Diagnosis 400 

CHAPTER  XXIV. 

Prognosis,  Prophylaxio,  and  Treatment. 

Mortality  . 401 

Prophylaxis 402 

Treatment 403 

General  Treatment  .      .      .   > 403 

Specific  Treatment 403 

Symptomatic  and  Special  Treatment 404 

The  Cure  of  Congenital  Syphilis 405 


PART   I. 

CHAPTER  I. 

HISTORY. 

For  nearly  four  centuries  the  medical  world  has  been  divided 
upon  the  subject  of  the  origin  of  s;v'philis.  Did  this  now  world-wide 
disease  have  its  beginning  in  the  dim  recesses  of  antiquity  to  be 
transmitted  in  an  uninterrupted  stream  to  modern  times,  or  was 
it  born  overnight,  as  it  were,  at  the  close  of  the  fifteenth  century? 
Was  syphilis  known  to  the  ancients,  or  did  Columbus'  men,  after 
their  long  forced  continence,  contract  it  from  the  native  women 
of  the  island  of  Espahola  and  introduce  it  into  Europe  upon  their 
return?  These  are  the  questions  which  have  vexed  syphilographers 
for  four  hundred  years,  and  in  spite  of  the  weight  of  authority  on 
both  sides  they  have  not  yet  been  answered  with  certainty. 

SYPHILIS  IN  THE  OLD  WORLD. 

Prehistoric  and  Ancient. — There  are  two  methods  of  approaching 
the  problem  of  the  origin  of  syphilis:  The  first  is  to  examine  the 
bones,  the  only  tissues  that  remain  of  people  of  a  former  age,  for 
evidence  of  the  disease.  The  second  method  is  to  study  the  T\Titings 
of  ancient  civilizations  for  mention  of  it. 

Bones. — In  making  a  study  of  bones  for  proof  of  the  origin  of 
lues  the  syphilographer  must  first  call  for  the  aid  of  geologists  or 
archeologists  to  establish  the  approximate  date  of  the  life  of  the 
individual  whose  remains  are  being  examined.  If  after  this  has  been 
done  pathologists  of  mature  and  reliable  judgment  agree  unquali- 
fiedly that  certain  abnormal  changes  in  the  bones  are  due  to  s\'philis, 
then,  and  only  then,  can  the  syphilographer  state  without  opposition 
that  syphilis  existed  at  a  certain  period. 

Buret,^  who  is  a  very  ardent  supporter  of  the  ancient  origin  of 
syphilis,  gives  an  account  of  the  discovery  at  Solutre,  in  1872, 
of  a  female  skeleton  which,  according  to  Broca,  Parrot  and  others, 

1  Syphilis  in  Ancient  and  Prehistoric  Times,  American  edition,  Philadelphia,  1891, 
p.  37. 

2 


18  HISTORY 

could  be  referred  to  the  Stone  Age,  and  in  the  tibiae  of  which  are  to 
be  found  unmistakable  evidences  of  syphilis.  These  are  in  the 
nature  of  exostoses,  and  are  particularly  well  marked  in  the  right 
tibia.  This  bone  shows  three  such  lesions  and,  according  to  Buret, 
were  examined  and  pronounced  syphilitic  by  such  eminent  authori- 
ties as  Broca,  Oilier,  Parrot,  and  the  great  Virchow  himself.  Buret 
cites  many  more  prehistoric  bones  which  he  claims  show  evidence  of 
syphilis. 

Edwards^  states  that  bones  from  the  Stone  Age  found  in  Japan 
show  probable  evidence  of  syphilis. 

In  direct  contradiction  of  these  statements,  Iwan  Bloch-  avows 
that  Virchow  repeatedly  declared  that  no  such  (syphilitic)  pre- 
Columbian  or  prehistoric  bone  was  known  to  him,  and  Bloch 
continues  that  it  is  quite  certain  that  no  such  bone  is  contained  in 
either  English  or  German  collections  or  museums. 

Writings. — That  syphilis  existed  in  the"  Old  World  centuries 
before  the  discovery  of  America  is  the  contention  of  Buret  and 
others,  and  they  cite  as  evidence  the  ancient  manuscripts  of  many 
countries. 

Chinese. — The  oldest  writings  quoted  are  those  of  China,  and  date 
back  to  the  year  2637  B.C.,  at  which  time,  according  to  the  manu- 
scripts translated  by  Captain  Dabry,  in  1863,  the  Emperor  Hoang-ty 
ordered  all  the  then  existing  documents  of  medicine  to  be  gathered 
together,  and  also  all  the  medical  lore  and  traditions  to  be  written 
on  parchment.  Then  with  this  data  in  his  possession  the  emperor 
wrote  the  renowned  medical  work  Hoang-ty-ni-king .  In  the  portion 
dealing  with  venereal  diseases  we  find,  says  Buret,^  that  the  Chinese 
knew  the  duality  of  the  chancre,  and  that  gonorrhea  and  syphilis 
were  separate  and  distinct  diseases.  The  chancre  was  described 
and  was  said  to  be  followed  by  headache,  with  fever,  pains  in  the 
bones,  cutaneous  manifestations,  and  lesions  of  the  mucous  mem- 
branes. Hereditary  syphilis  was  known,  and  as  treatment  mercurial 
frictions  were  prescribed. 

Buret  continues  his  quotations  from  early  writings  of  the  Japanese, 
the  Egyptians,  the  Assyrians  and  Babylonians,  the  Hindoos,  the 
Hebrews,  the  Greeks  and  the  Romans,  and  points  out  that  diseases 
and  sjonptoms  described  therein  are  syphilis. 

Japanese. — The  Japanese  manuscript  which  furnishes  the  most 
evidence  is  one  similar  to  the  Chinese  treatise  of  Hoang-ty,  which 
was  prepared  for  the  Emperor  Heizei-Tenno  by  his  two  physicians 
in  the  year  a.d.  808.    This  work  was  lost  or  stolen  soon  after  its 

'  Principles  and  Practice  of  Medicine,  New  York,  1909,  p.  253. 

2  Power  and  Murphy:  System  of  Syphilis,  London,  1908,  i,  p.  8. 

3  Syphilis  in  Ancient  and  Prehistoric  Times,  American  edition,  Philadelphia, 
1891,  p.  61. 


SYPHILIS  IN   THE  OLD  WORLD  19 

preparation  and  remained  in  obscurity  until  1827,  when  it  was 
discovered  by  a  shopkeeper  at  Bungo.  In  this  manuscript,  according 
to  Buret,  it  is  clearly  shown  that  the  Japanese,  at  this  early  date, 
were  fully  alive  to  most  of  the  lesions  of  syphilis. 

Egyptian. — In  the  early  inscriptions  and  papyri  of  the  ancient 
Egyptians,  Buret  finds  evidence  of  syphilis,  but  admits  that  from 
these  alone  it  would  be  impossible  to  draw  definite  conclusions. 
However,  he  states  that  when  we  remember  the  Hebrews  dwelt 
for  many  years  among  the  Egyptians  and  that  the  Hebrews  had 
syphilis,  no  doubt  remains. 

Hebrew. — To  prove  the  existence  of  syphilis  among  the  Hebrews, 
Buret  quotes  extensively  from  the  Bible.  The  account  of  the 
journey  of  Abram  and  his  beautiful  wife,  Sarai,  to  the  court  of 
Pharaoh  is  taken  as  proof  of  the  existence  of  syphilis  at  that  time. 
"And  the  Lord  plagued  Pharoah  and  his  house  with  great  plagues 
because  of  Sarai,  Abram's  wife."^  The  story  of  the  death  of  David's 
first  son  by  Bath-Sheba,  after  seven  days  of  life,  and  David's 
,  subsequent  lamentations  concerning  his  ailments,  especially  the 
condition  of  his  bones,  is  set  forth  by  Buret  to  prove  that  the  author 
of  the  Psalms  contracted  syphilis  from  the  wife  of  Uriah.  Many 
other  passages  of  Scripture  are  cited,  and  while  they  are  most 
convincing  of  the  presence  of  venereal  disease  in  this  race,  that 
syphilis  existed  is  not  beyond  dispute. 

Hindoo. — From  that  portion  of  the  Hindoo  Vedas,  the  Ayurveda, 
which  is  devoted  to  medicine,  are  quoted  many  passages  which 
purport  to  show  that  syphilis  existed  in  India  from  remote  antiquity. 
Certainly,  some  of  these  writings  describe  symptoms  which  can 
readily  be  assigned  to  lues.    Such  is  the  following  passage:  "The 

shameful   diseases    number  forty-four:  the  round  ulcer,  the 

prominent  pustule,  the  stone-like  excrescence,  the  alterations 

of  the  nails,  the  pustules  of  the  head,  the  bubo, the  ulcerations 

of  the  feet,  the  alopecia,  the  papules  of  youth, the  stricture  of 

the  anus ."-    Others  are  quoted  by  Buret,  but  apparently  add 

nothing  to  the  evidence  of  the  existence  of  syphilis. 

Grecian. — In  passing  from  Asiatic  and  African  to  early  European 
civilization  we  find  in  the  writings  ascribed  to  Hippocrates,  the 
great  Father  of  Medicine,  several  passages  which  can  readily  be 
taken  to  refer  to  syphilis.  In  the  chapter  of  Aphorisms  (Lecture  III, 
section  21)  is  found  the  following:  "In  summer  occur — opthalmias, 
pains  in  the  ears,  ulcerations  of  the  mouth  {aroiiaTojp  eX/ccoo-tes),  and 
rotting  of  the  genitals  {arjwedoves  aLdoiwv)." 

Many  other  Greek  writers,  medical  and  lay,  both  those  who  lived 

1  Genesis,  xii,  17. 

-  Buret:  Syphilis  in  Ancient  and  Prehistoric  Times,  American  edition,  Philadel- 
phia, 1891,  p.  119. 


20  HISTORY 

before  and  those  who  Hved  after  the  beginning  of  the  Christian 
era,  might  be  mentioned  as  furnishing  evidence  of  the  antiquity 
of  syphilis,  but  after  a  careful  perusal  of  those  quoted  by  Buret 
the  author  is  of  the  opinion  that  they  furnish  nothing  additional. 

Roman. — Of  the  Latin  writers  one  of  the  most  celebrated 
physicians  was  Celsus,  who  lived  in  the  first  century  before  Christ. 
He  writes  "Fungo  quoque  simile  ulcus  in  eadem  sede  (anus  vel  os 
vulvae)  nasci  solet.""^  Buret^  insists  that  the  author  refers  to  papulo- 
hypertropic  syphilides,  not  vegetations,  which  are  not  ulcerated, 
and  certainly  not  to  cancer,  as  Celsus  describes  this  malady  quite 
well  in  another  place,  stating  that  it  rarely  is  observed  except  in  the 
old. 

The  work  of  Galen,  the  great  Greek  physician,  who  practised  in 
Rome,  contains  much  that  might  refer  to  syphilis,  but  nothing 
absolutely  convincing. 

Other  Roman  writers,  Pliny,  Horace  and  Juvenal,  describe  dis- 
eases of  venereal  origin  which  can,  without  any  stretch  of  the 
imagination,  be  called  syphilis.  Catullus  denounces  the  mighty 
Csesar  as  a  sodomist,  and  accuses  him  and  his  companion,  Mamm-ra, 
of  having  "contracted  a  disease  whose  marked  spots  have  left 
upon  their  bodies  stains  which  will  not  disappear."^ 

Medieval. — It  has  been  pointed  out  in  the  foregoing  paragraphs 
that  there  is  some  evidence  of  the  existence  of  syphilis  in  the  old 
world  both  in  prehistoric  ages  and  in  times  of  which  we  have  records. 
Certainly,  there  can  be  no  doubt  of  the  existence  of  venereal  dis- 
eases, but  there  was  obviously  no  clear-cut  understanding  of  these 
disorders. 

From  the  time  of  the  fall  of  the  Roman  Empire  in  a.d.  312  to 
about  the  close  of  the  fifteenth  century  all  knowledge  was  more 
or  less  curtailed.  The  various  peoples  were  almost  continuously  at 
war,  licentiousness  and  vice  ran  riot,  while  the  practice  of  medicine 
advanced  but  little.  It  is  true  that  during  this  period  there  were  a 
number  of  men  whose  names  stand  out  prominently,  like  beacons 
in  the  night,  from  among  the  vast  throng  of  charlatans,  magicians, 
and  professional  poisoners  in  whose  hands  the  therapeutic  practices 
of  the  times  were  mostly  found.  But  these  men  failed  to  add  much 
to  medical  knowledge;  they  merely  preserved  for  posterity  the 
teachings  of  their  predecessors.  While  the  loose  morals  of  the  age 
were  certainly  provocative  of  venereal  disease,  most  of  the  phy- 
sicians failed  to  grasp  the  opportunity  to  study  these  maladies. 
If  syphilis  did  exist  it  was  not  usually  of  the  virulent  type  noted 
later. 

1  An  ulcer  resembling  a  fungus  growth  may  occur  in  these  same  parts  (the  anus 
or  entrance  of  the  vulva). 

2  Buret:  Ibid.,  p.  163.  ^  Ibid.,  p.  181. 


SYPHILIS  IN  THE  OLD  WORLD  21 

So  when  the  malady  broke  out  in  virulent  epidemic  form  during 
the  closing  years  of  the  fifteenth  century  it  was  considered  by  many 
to  be  an  entirely  new  disease. 

It  is  generally  conceded  that  it  was  during  the  siege  of  Naples, 
in  1497,  that  syphilis  reached  the  height  of  its  intensity;  but  it  is 
still  a  moot  point  whether  it  was  endemic  in  Europe  and  only 
developed  a  greater  virulence  and  was  propagated  more  rapidly  at 
that  time,  or  whether  it  was  absolutely  a  new  disease  to  the  Old 
World,  having  been  introduced  by  Columbus'  men. 

New  World  Origin., — The  earliest  published  mention  of  the 
New  World  as  the  cradle  of  syphilis  was  by  Leonard  Schmaus,  in 
1518.  According  to  Buref^  he  was  stimulated  to  make  this  state- 
ment by  Nicholas  Poll,  who  had  written,  in  1517,  that  guaiac,  which 
came  from  the  newly  discovered  island,  was  a  cure  for  venereal 
disease.  Buret  fails  to  mention  the  writings  of  Diaz  de  Isla,  a 
physician  of  Barcelona,  Seville  and  Lisbon.  His  account  of  syphilis 
was  written  in  1510,  but  was  not  published  until  some  years  later. 
In  this  account  the  Spanish  physician  states  that  the  "disease  of 
the  island  of  Espahola"  was  an  entirely  new  disease  in  Barcelona, 
introduced  by  Columbus'  men  in  1493.  This  statement  Bloch^ 
considers  as  final,  and  "with  one  blow  rends  the  veil  which  has 
covered  the  origin  of  syphilis." 

Karl  Sudhoff,  by  his  brilliant  researches,  has  thrown  much  light 
upon  this  vexing  problem.  This  eminent  medical  historian  shows 
that  the  Gotteslasterer  Edict  (the  edict  against  Blasphemers),  of 
Emperor  Maximilian  I,  issued  August  7,  1495,  refers  to  syphilis, 
but  does  not  mention  it  in  connection  with  the  Siege  of  Naples. 
However,  he  points  out  that,  according  to  Guicciardini,  there  was 
no  siege,  but  that  Charles  VIII  marched  through  Naples  without 
interference,  on  February  21,  1495,  and  did  not  leave  Novara  until 
October  10,  over  two  months  subsequent  to  the  issuance  of  the 
Gotteslasterer  Edict.  This  edict,  as  Sudhoff  points  out,  proves 
that  syphilis  was  well  known  in  Germany  in  July  and  could  not 
have  been  spread  by  Charles'  men.  Sudhoff  further  shows  that, 
contrary  to  the  belief  of  some,  the  physicians  of  the  time  had  quite 
a  thorough  knowledge  of  the  therapeutics  of  syphilis,  prescribing, 
among  other  remedies,  inunctions  of  mercury. 

Evidences  of  Prehistoric  Syphilis. — Many  investigators  have 
attempted  to  show  the  existence  of  syphilis  in  America  before  the 
advent  of  Columbus  both  by  archeological  and  philological  studies. 

A  number  of  writers  have  reported  the  finding  of  bones  in  America 
which  are  ascribed  to  a  date  prior  to  the  coming  of  the  Europeans, 
and  are  alleged  to  show  signs  of  syphilis.    Probably  the  most  notable 

1  Syphilis  in  the  Middle  Ages  and  in  Modern  Times,  American  edition,  Philadel- 
phia, 1895,  p.  157. 

2  Power  and  Murphy:  System  of  Syphilis,  London,  1908,  i,  p.  12. 


22  HISTORY 

are  those  discovered  by  Jones  and  reported  in  1876  in  the  Smith- 
sonian Contributions.  Here,  as  elsewhere,  archeologists  disagree 
as  to  the  date  of  the  graves  from  which  the  bones  were  taken, 
and  pathologists  of  note  did  not  agree  as  to  the  nature  of  the 
pathological  processes. 

Phylological  studies  of  the  many  Indian  dialects  reveal  the  fact 
that  in  each  of  these  dialects  there  was  a  primitive  term  for  syphilis, 
and  that  there  was  no  evidence  of  recent  coinage. 

Epidemic  of  Naples. — Whether  we  accept  the  Old  World  or  the 
New  World  as  the  original  home  of  syphilis,  it  is  beyond  dispute 
that  following  the  invasion  of  Italy  by  Charles  VIII  there  was  a 
rapid  spread  of  the  disease  over  all  Europe.  And  while  it  was  in 
reality  a  pandemic,  it  has  been  styled  the  Epidemic  of  Naples. 
As  has  been  pointed  out,  syphilis  manifested  a  very  exaggerated 
course  at  that  time.  It  was,  however,  in  all  probability,  compli- 
cated by  other  diseases,  but  notwithstanding  this  many  physicians 
soon  described  with  fair  accuracy  its  lesions  and  symptoms. 

One  of  the  earliest  of  these  was  Niccolo  Leoniceno  (1428-1524), 
who,  in  1497,  published  a  treatise  on  this  disease. 

However,  the  most  distinguished  man  of  this  period  to  lend  his 
name  to  the  advancement  of  the  knowledge  of  syphilis  was  Para- 
celsus (1493-1541).  This  eminent  physician  was  the  first  to  assert 
that  lues  could  be  transmitted  from  parent  to  offspring. 

NOMENCLATURE. 

The  appellations  given  to  this  disease  of  the  ages  are  almost 
as  numerous  as  its  lesions.  In  the  early  days  of  the  recognition  of 
syphilis,  that  is,  in  the  closing  years  of  the  fifteenth  and  the  opening 
years  of  the  sixteenth  centuries,  the  name  of  the  country  in  which 
it  was  supposed  to  have  had  its  origin  was  applied.  Also  the 
various  peoples  used  the  name  of  the  country  of  their  enemies. 
Thus  Morbus  gallicus  was  used  by  the  Germans,  Spaniards,  and 
Italians,  while  the  French,  wishing  to  shift  the  blame  of  its  origin 
from  themselves,  called  it  Morbus  neapolitanus,  although  at  quite 
an  early  date  they  used  the  term  la  grosse  verole.  Among  the 
Spaniards  it  was  popularly  known  as  hubas,  and  it  was  also  known 
as  Turkish,  German  and  Polish  pox.  From  its  supposed  American 
origin  it  was  termed  by  Diaz  de  Isla  the  "  disease  of  the  island  of 
Espafiola."  In  this  connection  it  may  be  noted  that  of  all  the 
names  applied  to  syphilis  by  the  native  Americans,  not  one  crept 
into  the  nomenclature  of  Europe. 

It  remained,  however,  for  the  Veronese  physician,  Girolamo 
Fracastoro  (1484-1553),  who  was  also  poet,  pathologist,  physicist, 
astronomer,  and  geologist,  to  give  to  this  disease  the  name  by  which 
it  is  known  almost  the  whole  world  over.    In  his  immortal  poem. 


NOMENCLATURE  23 

"Syphilus  sive  Morbus  Gallicus,"  published  in  1530,  Fracastoro 
tells  of  a  shepherd,  Syphilus  by  name,  who,  in  a  fit  of  anger  on 
account  of  a  drought  which  destroyed  many  of  his  sheep,  denounced 
the  gods  and  set  up  altars  to  the  king.  In  revenge  a  scourge  was 
sent  upon  the  people,  Syphilus  being  the  first  one  attacked,  and 
"this  terrible  disease — known  since  then  among  us  by  the  name  of 
Syphilis — does  not  take  long  to  spread  to  our  entire  nation,  not  even 
sparing  our  King  himself."^ 

The  history  of  syphilis  from  the  time  of  Fracastoro  to  that  of  John 
Hunter  is  practically  the  history  of  medicine.  There  is  scarcely 
a  name  with  which  is  connected  any  advancement  of  the  healing 
art  but  is  found  in  the  syphilology  of  these  years. 

John  Fernel  (1496-1558)  pointed  out  the  necessity  of  an  abrasion 
of  the  epidermis  for  the  syphilitic  virus  to  gain  entrance  to  the 
body.  He  also  showed  the  relationship  between  the  chancre  and 
the  general  infection. 

Gabrille  Fallopio  (1523-1562),. who  was  primarily  an  anatomist, 
and  whose  name  still  clings  to  anatomical  nomenclature  (Fallopian 
tubes),  also  wrote  about  syphilis,  and  believed  that  syphilis  of  the 
viscera  and  bones  was  due  to  mercury.  He  was  therefore  bitterly 
opposed  to  its  use. 

Jean  Astruc  (1684-1766),  in  1736,  published  his  De  morhis 
venereis,  which  was  a  comperidium  of  the  understanding  of  syphilis 
of  the  times.  Astruc  was  a  firm  believer  in  the  American  origin  of 
of  syphilis,  and  in  this  work  proved  it  to  his  own  satisfaction. 

John  Hunter  (1728-1793).  Probably  no  other  name  in  all  the 
history  of  medicine  stands  out  more  prominently  than  that  of  John 
Hunter.  Great  beyond  his  time  as  a  surgeon,  he  undoubtedly 
retarded  the  knowledge  of  syphilis  many  decades.  Convinced  of 
the  unity  of  syphilis  and  gonorrhea.  Hunter  inoculated  himself 
on  the  glans  and  prepuce  with  gonorrheal  pus.  When  a  chancre 
developed,  followed  by  constitutional  syphilis,  he  considered  it 
proof-positive  of  the  truth  of  his  contentions.^ 

While  this  experiment  of  Hunter's  and  his  false  interpretation 
of  it  dominated  syphilology  until  Ricord  disproved  it,  a  few  men 
disagreed  with  the  great  surgeon  and  had  the  courage  of  their  con- 
victions. Among  these  may  be  mentioned  Benjamin  Bell  (1749- 
1806),  who  in  his  work  on  venereal  diseases  maintained  the  duality 
of  syphilis  and  gonorrhea.^ 

Phillippe  Ricord  (1800-1889).  Wherever  syphilis  is  studied  will 
be  felt  the  influence  of  the  work  of  Phillippe  Ricord,  and  with  him 
it  may  be  said  began  the  modern  knowledge  of  syphilis.  He  was 
described  by  Oliver  Wendell  Holmes  as  "the  Voltaire  of  pelvic 

1  Fracastor's  Syphilis:  St.  Louis,  1911,  p.  55. 

2  Hunter:  A  Treatise  on  Venereal  Disease,  Philadelphia,  1859,  p.  432. 

3  Bell:  Treatise  on  Gonorrhea  Virulenta  and  lues  Venerea,  Edinburgh,  1793,  ii. 


24  HISTORY 

literature — a  skeptic  as  to  the  morality  of  the  race  in  general, 
who  would  have  submitted  Diana  to  treatment  with  his  mineral 
specifics  and  ordered  a  course  of  blue  pills  for  the  vestal  virgins." 
This  great  syphilologist,  by. over  2500  inoculations,  proved  con- 
clusively the  duality  of  syphilis  and  gonorrhea,  although  he  did 
not  consider  that  the  latter  possessed  a  specific  virus. ^ 

Ricord  will  also  long  be  remembered  for  his  division  of  the  mani- 
festations of  syphilis  into  three  stages.  This  division  has  been 
accepted  and  followed  by  most  syphilographers  up  to  the  present 
time. 

According  to  Ricord,  syphilis  begins  with  the  primary  stage, 
which  includes  the  chancre  and  the  adjacent  adenopathy.  This  is 
followed  by  the  so-called  secondary  stage,  when  the  disease  becomes 
general  and  the  various  cutaneous  and  other  lesions  are  manifest. 
During  the  third,  or  tertiary,  stage  the  bones  and  deep  viscera 
become  involved.  Ricord  believed  that  only  during  the  primary 
stage  was  syphilis  inoculable,  but  that  during  the  secondary  stage 
it  was  transmissible  to  the  offspring.  During  the  tertiary  stage 
it  was  neither  inoculable  nor  transmissible.  He,  however,  later 
retracted  these  views  in  part  and  L,dmitted  that  in  the  secondary 
stage  syphilis  was  inoculable.  Ricord  described  vaginal  and 
uterine  chancres  and  pointed  out  that  in  certain  cases  in  which  no 
chancre  is  discovered  the  lesion  is  probably  located  in  the  urethra.^ 

It  would  be  impossible  even  to  mention  the  names  of  all  the  men 
who  have  contributed  to  the  knowledge  of  syphilis  since  Ricord 
showed  the  way.  Such  leaders  as  Virchow  and  Fournier  lent  the 
aid  of  their  master  minds  to  the  elucidation  of  its  problems.  The 
modern  renaissance  of  syphilis,  however,  may  be  said  to  have  begun 
with  the  epoch-making  work  of  Metchnikofl  and  Roux,^  who  in 
1903  succeeded  in  transmitting  this  disease  to  monkeys.  Then 
followed,  in  rapid  succession,  the  finding  of  the  infecting  organism 
by  Schaudinn,*  the  announcement  of  the  complement-fixation  test 
for  syphilis  by  Wassermann,^  the  discovery  of  salvarsan  by  Ehrlich,'' 
the  cultivation  of  the  Treponema  pallidum,'^  the  use  of  cultures 
for  diagnostic  purposes  by  Noguchi,^  the  intraspinal  injection  of 
salvarsanized  serum  in  the  treatment  of  syphilis  of  the  nervous 
system  by  Swift  and  Ellis,^  and  finally  the  demonstration  of  the 
organism  of  syphilis  in  the  brains  of  paretics  and  the  spinal  cords 
of  tabetics  by  Noguchi  and  Moore. ^^ 

'  Ricord:  Traite  pratique  des  maladies  veneriennes,  Paris,  1839. 

^  Ricord:  Letters  on  Syphilis,  American  edition,  Philadelphia,  1857,  p.  101. 

3  Ann.  de  I'Inst.  Pasteur,  1903,  xvii,  p.  809.  / 

■•  Arb.  a.  d.  k.  Gsndhtsamte,  1905,  xxii,  p.  527. 

s  Deutsch.  med.  Wchnschr.,  1906,  xxxii,  p.  745. 

8  Die  experimentelle  Terapie  der  Spirillosen,  Berlin,  1910. 

'  Noguchi:  Jour.  Exper.  Med.,  1911,  xiv,  p.  99.  *  Ibid.,  p.  557. 

9  New  York  Med.  Jour.,  1912,  xcvi,  p.  53. 
1"  Jour.  Exper.  Med.,  1913,  xvii,  p.  232. 


CHAPTER   II. 
IMPORTANCE    OF    SYPHILIS. 

Geographical  Distribution. — One  of  the  most  striking  features 
of  syphilis  is  its  world-wide  distribution.  There  is  scarcely  a  spot  on 
the  globe  where  human  beings  reside  which  has  not  harbored  this 
ubiquitous  disease.  It  is  found  in  the  gold  camps  of  the  Yukon 
and  among  the  ivory  hunters  of  the  Congo;  on  the  vast  steppes  of 
Siberia  and  the  plains  of  Argentine.  It  is,  however,  especially  a 
disease  of  dense  population,  whether  temporary  or  permanent. 
In  the  great  cities  of  the  world,  London,  Paris,  New  York,  Berlin, 
syphilitics  are  numbered  by  the  thousands,  and  such  multitudes  as 
gather  together  for  great  fairs  and  expositions  as  Nijni-Novgorod, 
Chicago  and  St.  Louis  leave  syphilis  in  their  wake. 

It  has  been  affirmed  that  Iceland  is  peculiarly  free  from  this 
disease.  If  such  is  the  case,  it  would  seem  that  this  is  due,  not  to 
the  geographical  situation,  but  to  the  simple  lives  and  morality  of 
the  inhabitants.  Livingston  has  stated  that  when  the  nativfes 
of  central  Africa  contract  syphilis  on  the  coast  it  disappears  without 
treatment  upon  their  return  inland.  This  statement  must  be  taken 
with  the  greatest  reserve,  for  it  is  a  well-known  fact  that  apparent 
spontaneous  cures  have  occurred  when  in  reality  the  disease  was 
lying  dormant. 

It  would  be  well-nigh  impossible  to  name  all  the  countries  in 
which  syphilis  is  found,  much  less  trace  the  source  of  the  disease 
for  each.  In  Europe,  Russia,  with  her  vast  hordes,  is  infected; 
Germany,  France,  and  Italy  contain  her  hot  beds  of  pollution; 
while  England,  with  her  great  cities,  harbors  syphilitics  in  immense 
numbers. 

Passing  to  Asia  we  find  the  disease  most  prevalent  in  China  and 
Japan,  where  crowded  districts  are  so  common.  In  the  United  States 
the  great  cities  New  York,  Chicago,  Philadelphia,  St.  Louis,  San 
Francisco,  and  the  lesser  ones,  even  dow^n  to  the  smallest  villages, 
contain  syphilis  to  a  greater  or  less  extent.  It  is,  however,  a  matter 
of  common  observance  among  physicians  of  certain  rural  districts 
that  syphilis  is  rarely  encountered.  The  author  has  talked  to  a 
number  of  them,  who  informed  him  that  in  the  course  of  several 
years'  practice  they  have  seen  but  one  or  two  cases. 

Prevalence  of  Syphilis. — It  will  be  seen  from  the  above  that 
syphilis  is  an  almost  omnipresent  disease,  and  yet  from  the  very 


26  IMPORTANCE  OF  SYPHILIS 

nature  of  it,  it  is  one  of  the  most  difficult  concerning  which  accurate 
statistics  may  be  obtained.  Many  estimates  as  to  the  prevalence 
of  syphilis  have  been  made,  those  of  Erb  and  Fournier  probably 
being  the  best  known.  The  former  considered  that  of  the  adult 
population  of  Berlin,  12  per  cent,  were  infected,  while  the  latter 
estimated  that  15  per  cent,  of  the  adult  population  of  Paris  had 
syphilis. 

In  December,  1912,  the  Department  of  Health  of  the  City  of 
New  York  sent  a  circular  letter  to  7000  physicians  of  Greater  New 
York,^  requesting  that  the  number  of  cases  of  venereal  disease 
seen  by  each  physician  during  the  past  year  be  reported.  Of  the 
7000  physicians  only  2217  replied,  and' they  reported  13,350  cases 
of  syphilis.  The  number  of  physicians  reporting  represents  less  than 
one-third  of  the  total  number  of  physicians  to  which  the  letter 
was  sent,  and  if  those  who  did  not  report  had  seen  as  many  syphilitics 
as  those  who  did  report  the  total  number  would  be  approximately 
40,000.  Estimating  the  population  of  Greater  New  York  at  about 
5,000,000,  the  number  infected  with  syphilis  is  seen  to  be  0.8  per 
cent,  of  the  entire  population.  The  author  considers  this  an 
exceedingly  low  figure,  because  there  are  many  syphilitics  who 
during  any  given  year  do  not  see  a  physician. 

Banks,^  after  examining  the  records  of  the  United  States  Marine 
Hospitals,  has  arrived  at  the  interesting  conclusion  that  2  per  cent, 
of  the  adult  males  of  the  United  States  are  syphilitic. 

In  our  present  state  of  advancement  in  municipal  and  State 
control  of  disease  it  would  be  impossible  to  make  a  complete  survey 
of  the  population  in  regard  to  syphilis;  but  it  is  possible,  with 
certain  units  of  population,  such  as  those  in  hospitals,  eleemosynary 
institutions,  penitentiaries,  etc.  Indeed,  such  investigations  have 
been  made,  especially  in  hospitals,  and  the  results  have  been  most 
instructive. 

For  example,  Hammond^  applied  the  Wassermann  reaction  to  the 
entire  population  of  the  New  Jersey  State  Hospital,  finding  6.3 
per  cent,  positive.  Lucas,^  by  examining  HI  cases  in  the  Children's 
Hospital  in  Boston,  found  31  per  cent,  were  syphilitic.  Southard^ 
reported  23  per  cent,  of  6000  Wassermann  tests  performed  in  the 
Harvard  Neuropathologic  Testing  Laboratory  were  positive.  He 
stated,' however,  that  the  cases  were  in  many  instances  selected 
because  likely  to  be  positive,  and  therefore  the  percentage  is 
undoubtedly  much  higher  than  it  otherwise  would  be. 

1  Monthly  Bulletin,  Department  of  Health,  City  of  New  York,  June,  1913,  p.  147. 

2  U.  S.  Public  Health  Reports,  February  26,  1915,  p.  618. 

3  Am.  Jour.  Insan.,  1913,  Ixx,  p.  107. 

*  Boston  Med.  and  Surg.  Jour.,  1913,  clxix,  p.  423. 
5  Ibid.,  1914,  clxx,  No.  25. 


(   I  V  f 


ECONOMIC  IMPORTANCE  27 

The  same  fact  applies  to  the  author's  series  performed  at  the 
Arkansas  State  Hospital  for  Nervous  Diseases,  where  33  per  cent, 
of  1000  tests  were  found  to  give  positive  reactions.  The  practice 
in  this  institution  was  to  make  serological  investigations  for  syphilis 
only  in  such  cases  as  gave  a  suspicious  history  or  upon  physical 
examination  showed  evidence  which  suggested  luetic  infection. 

Of  all  the  social  units  the  military  services,  army  and  navy, 
present  possibly  the  best  field  for  investigation  into  the  prevalence 
of  syphilis,  for  in  these  services  the  individuals  are  kept  under  more 
or  less  strict  surveillance.  In  the  British  Army^  the  admission  for 
syphilis  per  1000  of  strength  varied  from  96.43  in  1869  to  179.37 
in  1886,  to  19.19  in  1908.  In  the  United  States  Army  the  figures 
have  never  reached  as  high  as  in  the  British  Army,  nor  have  they 
gone  so  low.  The  highest  number  of  admissions  for  syphilis  per 
1000  was  in  1867,  when  the  figures  were  117,  while  the  lowest 
mark  was  reached  in  1908,  when  there  were  but  19.99  per  1000.  In 
his  report  for  the  year  1914^  the  Surgeon-General  of  the  United 
States  Army  says,  "  From  recent  investigations  it  is,  indeed,  probable 
that  the  frequency  of  venereal  diseases  among  our  soldiers  is  less 
than  among  adult  males  in  the  cities  of  this  country.  ' 

This  statement  is  based  upon  an  extensive  Wassermann  survey 
made  by  Vedder.^  This  investigator  found  that  16.77  per  cent,  of 
recruits  are  undoubtedly  syphilitic,  and  estimates  that  fully  20 
per  cent,  of  the  young  men  of  the  country  of  the  general  class  from 
which  recruits  come  are  infected.  Of  the  white  enlisted  men  of  the 
army  he  found  16.08  per  cent,  syphilitic.  Of  the  West  Point  cadets, 
2.57  per  cent,  gave  very  strongly  positive  Wassermann  tests,  while 
2.89  gave  less  strongly  positive  tests,  from  which  Vedder  estimates 
that  5  per  cent,  of  the  young  men  of  the  country  of  the  college- 
student  class  are  syphilitic. 

Economic  Importance. — While  syphihs,  as  a  rule,  especially  in  the 
early  periods,  is  not  a  disease  to  incapacitate  its  victim  for  work, 
it  may  pursue  its  insidious  course  until  the  vital  organs  are  attacked, 
and  in  one  way  or  another  rob  the  individual  of  his  ability  to  gain  a 
livelihood.  It  is  probable,  however,  that  nearly  every  syphilitic 
loses  some  time  from  his  accustomed  vocation  even  in  the  earliest 
stages  of  the  disease. 

In  the  United  States  Army  the  total  number  of  days  lost  on 
account  of  syphilis  during  the  year  1913  was  38,597,  which  represents 
a  monetary  value  of  approximately  $53,000.  In  those  conditions 
caused  by  syphilis  which  have  been  designated  as  parasyphilitic, 

1  Power  and  Murphy:  System  of  Syphilis,  London,  1910,  vi,  p.  29. 

2  Surgeon-General's  Report,  1914,  p.  12. 

5  The  Prevalence  of  Syphilis  in  the  Army,  Bull.  No.  8,  War  Department,  Washing- 
ton, 1915. 


28  IMPORTANCE  OF  SYPHILIS 

of  course  the  economic  loss  is  much  greater.  Tabetics,  as  a  rule, 
are  unable  to  perform  their  accustomed  work,  while  paretics  not 
only  are  unable  to  perform  their  accustomed  work,  but  very  fre- 
quently in  attempting  to  do  so  make  grave  financial  errors  and 
cause  great  loss  to  themselves  or  their  employers. 

The  old  adage  that  ''syphilis  never  kills"  is,  of  course,  false, 
and  while  it  is  true,  it  is  most  rare  nowadays  to  see  deaths  due  to 
acquired  syphilis  in  the  acute  stages;  yet  there  are  many  deaths 
each  year  that  are  undoubtedly  hastened  by  this  disease  and  also 
many  deaths  which  can  be  attributed  directly  to  its  later  mani- 
festations. Congenital  syphilis  also  causes  many  deaths  of  infants 
and  kills  in  utero  many  others. 

Ravogli^  collected  statistics  from  the  Cincinnati  City  Hospital 
from  1888  to  1907,  and  found  that  of  100,713  patients  and  9705 
deaths  only  168  were  caused,  by  syphilis.  In  the  United  States 
Army  of  about  81,000  men  there  were  397  deaths  due  to  all  causes 
during  the  year  1913,  and  out  of  these  only  5  were  due  to  syphilis 
and  its  results.^ 

According  to  the  mortality  statistics  of  the  Bureau  of  the  Census 
the  number  of  deaths  from  syphilis  m  the  registration  area  of  the 
United  States  during  the  year  1913  was  4589.  Deaths  from  paresis 
amounted  to  4371,  while  tabes  claimed  1674,  making  a  total  of 
10,734  deaths  directly  due  to  syphilis.  The  total  for  1912  was 
9582;  for  1911,  8433;  and  for  1910,  7600.  Typhoid  fever  killed  but 
11,323  in  1913,  while  smallpox,  once  the  scourge  of  the  race, 
destroyed  only  125  persons  during  the  same  period.  The  regis- 
tration area  of  the  United  States  comprises  about  two-thirds  of  the 
entire  population,  so  it  may  readily  be  seen  that  if  the  registration 
area  is  representative  of  the  whole  country,  and  there  is  no  reason 
to  think  to  the  contrary,  the  total  number  of  deaths  from  syphilis 
in  the  United  States  for  the  years  given  above  were  as  follows: 

1910  ......   10,132 

1911 11,244 

1912 12.776 

1913 16,101 

In  all  probability  these  figures  are  too  low,  as  many  physicians 
do  not  report  deaths  due  to  syphilis  out  of  deference  to  the  relatives 
of  the  deceased,  and  undoubtedly  many  deaths  from  syphilis  occur 
when  an  error  in  diagnosis  has  been  made.  In  the  year  1913  there 
were  87,755  deaths  reported  as  due  to  organic  heart  disease  and 
certainly  in  a  large  percentage  of  these  the  heart  disease  was  caused 
by  syphilis.     It  is  probable  that  the  increase  in  the  number  of 

1  Syphilis,  New  York,  1907,  p.  147. 

2  Surgeon-General's  Report,   1914,  pp.  221-222. 


ECONOMIC  IMPORTANCE  29 

deaths  from  syphilis  shown  from  1910  to  191 3  was  due,  in  a  measure 
at  least,  to  more  correct  diagnosis  being  made.  However,  the  fact 
remains  that  an  appalling  number  of  deaths  from  syphilis  do  occur, 
that  the  number  of  persons  suffering  from  syphilis  is  in  some 
localities  as  high  as  1  per  cent,  of  the  entire  population,  and  that 
the  economic  loss  to  the  nation  is  almost  beyond  compute. 

The  statement  of  an  eminent  foreign  visitor  to  the  International 
Congress  of  Hygiene  and  Demography  in  Washington  in  1912,  after 
visiting  the  prominent  medical  centres  of  the  country,  that  in  none 
of  the  clinics  of  Europe  was  there  so  much  syphilis  as  he  saw  in  the 
United  States ;  and  that  if  measures  were  not  taken  for  its  suppres- 
sion it  would  soon  cause  marked  deterioration  of  the  race,  certainly 
furnishes  food  for  thought.  Aside  from  the  deaths  caused  directly  by 
syphilis,  aside  from  the  abortions  it  claims,  aside  from  the  physical 
suffering  it  entails,  no  other  disease  has  evoked  so  much  mental 
agony,  both  to  those  who  have  contracted  it  through  immoral  acts 
and  to  its  innocent  victims,  and  also  to  those  near  and  dear  to 
the  sufferers.  This  mental  anguish  alone  undoubtedly  has  very 
materially  lessened  the  effectiveness  of  the  individual  and  not 
infrequently  has  driven  its  victim  to  a  suicide's  grave. 


CHAPTER    III. 
ETIOLOGY. 

EARLY  VIEWS. 

It  is  not  surprising  that  primitive  man  before  the  dawn  of 
civihzation  laid  at  the  door  of  the  angered  gods  or  evil  spirits  the 
blame  for  the  causation  of  disease.  But  some  of  the  beliefs  concern- 
ing the  cause  of  syphilis  which  gained  credence  during  the  year 
following  the  opening  of  the  sixteenth  century  are  most  astounding. 
At  this  period  astrologers  were  much  in  vogue,  and  we  find  that 
by  many  syphilis  was  ascribed  to  various  astrological  observations. 
For  example,  Steber  wrote,  in  1494,  of  a  new  disease  caused  by 
conjunction  of  planets.  Carl  Sudhoff^  quotes  from  a  manuscript 
of  Paul  von  Middelburg  in  which  he  prophesied  concerning  the  con- 
junction of  Mars,  Jupiter,  and  Saturn  in  the  sign  of  the  Scorpion  on 
November  25, 1484,  and  that  the  earth  would  be  visited  by  a  horrible 
venereal  disease  which  would  be  most  severe  about  1492-1500. 

Other  absurd  views  were  held.  Nicolo  Leoniceno  believed  that 
syphilis  could  be  ascribed  to  the  heavy  rains  and  overflow  of  the 
rivers  which  occurred  in  1494.  Fallopius  thought  the  wells  of  Naples 
were  poisoned  by  the  Spaniards,  and  that  they  had  plaster  placed 
in  the  bread  which  acted  as  causes  of  the  disease.  Paracelsus  con- 
sidered syphilis  a  sort  of  bastard  offspring  of  leprosy  and  buboes, 
and  Van  Helmont  wrote  that  it  came  from  sodomy  with  a  mare 
diseased  of  farcy.  This  Ricord  considered  as  at  least  possible.^ 
A  theory  which  held  sway  at  various  times,  and  has  had  numerous 
advocates,  was  that  by  having  intercourse  with  a  number  of  men  a 
healthy  woman  could  develop  lues  through  a  multiplicity  of  male 
elements.  Btit  of  all  the  alleged  causes  of  syphilis  the  most  gruesome 
was  that  advanced  by  Fioraventi,  who  considered  the  disease  to  be 
due  to  eating  human  flesh.  He  further  claimed  to  have  produced 
it  in  animals  by  experimentation. 

Finally,  however,  with  the  advance  of  knowledge  these  grotesque 
ideas  gave  place  to  more  rational  views,  and  we  find  Hunter^ 
speaking  of  the  syphilitic  ''poison"  and  Ricord*  writing,  "this 
poison  may  at  present  be  called  by  its  name;  that  is,  the  syphilitic 
virus." 

1  Aus  der  Friihgeschichte  der  Syphilis,  Leipzig,  1912. 

2  Ricord:  Letters  on  Syphilis,  American  edition,  Philadelphia,  1857,  pp.  98-99. 

3  A  Treatise  on  Venereal  Diseases,  American  edition,  Philadelphia,  1859.  p.  41. 
*  Letters  on  Syphilis,  American  edition,  Philadelphia,  1857,  p.  99. 


MICROBIOLOGY  31 


MICROBIOLOGY. 


Historical. — The  Jesuit  priest  Athanasius  Kircher  (1602-1(580) 
was  the  first  to  state  a  belief  in  microorganisms  as  the  cause 
of  disease.  With  the  crude  microscope  of  his  time  he  examined  the 
blood  of  patients  sick  with  plague  and  saw  what  he  called  "worms" 
in  countless  numbers.  As  pointed  out  by  Frederick  Loeffler/ 
these  were  probably  rouleaux  of  red  blood  cells  and  not  micro- 
organisms. Other  microscopists  followed  Kircher,  who  undoubtedly 
saw  the  larger  bacteria  and  protozoa.  Notably  among  these  was 
Antonj  van  Leuwenhoek  (16.32-1723),  the  Dutch  linen  draper, 
who  possessed  some  419  lenses,  most  of  which  he  ground  himself. 
The  work  of  these  men  stimulated  the  belief  in  the  microbiological 
causes  of  disease;  but  it  was  left  to  Marcus  Anton  von  Plinciz,  Sr. 
(1705-1786),  to  express  the  belief,  in  1762,  that  each  disease  has 
its  special  seminium  verminosum. 

However,  it  was  over  a  century  later,  in  1863,  that  a  specific 
microorganism  was  proved  to  be  the  cause  of  disease.  In  this  year 
Davine  showed  that  the  small  rod-shaped  bodies  described  by 
Pollender  in  1855,  and  found  in  the  blood  and  spleen  of  animals 
dead  of  anthrax,  would  produce  the  disease  in  healthy  animals. 

Following  the  discovery  of  the  anthrax  bacillus  a  renewed  and 
diligent  search  was  made  in  all  syphilitic  lesions  for  an  organism 
which  might  be  ascribed  to  this  disease.  Donne,  as  far  back  as 
1837,  found  in  chancres  certain  minute  spiral  bodies  which  he  at 
first  thought  might  be  the  causative  factor  in  syphilis,  but  later,  in 
1844,  expressed  the  view  that  they  were  accidental. 

Many  were  the  workers  in  the  field  and  many  were  the  organisms 
described.  But  few  of  them,  however,  created  much  credence  in 
the  scientific  world  until  1884,  when  Lustgarten,^  working  under 
the  guidance  of  Weigert,  announced  the  discovery  by  a  special 
staining  technic  of  a  small  slelider  bacillus  in  indurated  chancres  and 
gummata.  This  organism  closely  resembled  the  bacillus  of  tuber- 
culosis, but,  unlike  the  latter,  could  not  be  cultivated. 

Many  investigators  attempted  to  confirm  the  work  of  Lustgarten, 
and  for  a  time  it  appeared  that  the  long-sought  goal  had  been 
attained.  However,  soon  after  the  publication  of  Lustgarten's 
second  paper,^  in  which  he  went  more  into  detail  concerning  the 
morphology  ahd  staining  characteristics  of  his  organism,  Alvarez 
and  TaveP  announced  that  they  had  been  unable  to  find  the  Lust- 
garten bacillus  in  many  syphilitic  lesions,  but  had  found  it  in  some, 

1  Volesungen  iiber  die  ^eschichtliche  Entwicklung  der  Lehre  von  den  Bacterien, 
Leipzig,    1887,   pp.   1,  2. 

2  Wiener  med.  Wchnschr.,  1884,  No.  47. 

'  Lustgarten:  Wien.  med.  Jahrbucher,  1885. 

*  Arch,  de  physiol.  norm,  et,  path.,  1885,  vi,  p.  .303. 


32  ETIOLOGY 

as  well  as  an  organism  identical  in  morphology  and  staining  in  the 
smegma  of  healthy  individuals. 

In  the  succeeding  years  numerous  other  workers  in  the  field  of 
microbiology  found  and  described  organisms,  which  they  considered 
the  etiological  factor  in  syphilis.  Thus,  Disse  and  Taguchi^  were 
convinced  that  the  encapsulated  diplococcus  they  had  isolated  from 
syphilitic  lesions  was  the  cause  of  the  disease.  They  even  went 
so  far  as  to  claim  that  their  cultures  developed  distinctive  specific 
lesions  when  inoculated  into  rabbits. 

Joseph  and  Piorkowsky^  attacked  the  problem  in  an  entirely 
original  manner.  By  the  use  of  fresh  human  placenta  and  semen 
from  syphilitic  individuals  they  obtained  in  pure  culture  a  bacillus 
which  they  thought  had  solved  the  problem.  But  when  a  number  of 
healthy  physicians  were  inoculated  with  these  organisms  with 
negative  results  they  were  forced  to  admit  their  error. 

Cytoryctes  Luis. — Early  in  1905  SiegeP  announced  the  finding 
of  a  small  protozoon  in  the  exudates  and  blood  of  patients  suffering 
with  syphilis  and  gave  to  it  the  name  Cytoryctes  luis. 

Treponema  Pallidum. — Siegel  was  very  enthusiastic  over  his 
discovery,  declaring  that  at  last  the  long-looked-for  germ  of  syphilis 
had  been  found,  and  to  a  certain  extent  his  enthusiasm  was  shared 
by  others.  So  much  was  this  so,  in  fact,  that  a  commission  was 
assembled  in  Berlin  to  confirm,  if  possible,  his  findings.  At  the  head 
of  this  work  was  placed  Schaudinn,  a  zoologist,  who,  although  a 
comparatively  young  man,  already  had  established  an  enviable 
reputation  for  himself  in  his  chosen  profession.  Associated  with 
him  in  this  work  was  E.  Hoffmann,  a  thoroughly  trained  syphilol- 
ogist.  These  two  scientists  attacked  the  problem  with  unlimited 
energy,  and  it  was  not  long  until  they  had  shown  that  Siegel's 
"cytoryctes"  was  not  a  protozoon  but  an  organic  artefact.  And 
while  by  so  doing  they  destroyed  the  hopes  of  some,  they  were 
destined  to  make  a  discovery  which  was  to  revolutionize  the  study 
of  syphilis. 

On  March  3,  1905,  a  young  woman  with  syphilis  of  ten  weeks' 
standing  was  examined.  A  chancre  of  the  left  labium  majus  and 
a  number  of  papules  of  the  vulva  were  found.  The  exudate  from  one 
of  the  latter  being  placed  under  the  microscope,  Schaudinn^  saw  a 
considerable  number  of  fine  spirilla,  and  the  parasite  of  syphilis 
had  been  discovered. 

The  news  of   this   epoch-making  work   soon   spread   over   the 

1  Deutsch.  med.  Wchnschr.,  1885,  No.  48;  1886,  No.  14.  Das  Contagium  der 
Syphilis,  Tokio,  1887. 

2  Berl.  klin.  Wchnschr.,  1902,  p.  257. 

3  Sitzengsberichte  der  kgl.  Preussischen  Akademie  der  Wissenschaften.  Physik. 
Mathem.  Klasse,  Berlin,  1905,  February  25. 

4  Arb.  a.  d.  k.  Gsndhtsamte,  1905,  xxii,  p.  527. 


PLATE  I 


A. 


Fig.  1. — Treponema  pallidum  from  ehanere,  stained  by  Levaditi's 
method.     X  ISOO. 

Fig.  2.— Treponema  pallidum  from  rabbit's  testicle,  stained  by  Leva- 
diti's method.      X  ISOO. 

Fig.  3. — Treponema  pertenue  from  ya^v,  stained  by  Levaditi's  method. 
X  IBOO. 

Fig.  A. — Spiroeheta  reeurrentis  from  blood  of  mouse.      X  lOOO. 


{Bulletin  No.  1,  Medical  Department,  United  States  Army.) 


MICROBIOLOGY  33 

scientific  world,  and  before  long  many  confirmations  of  it  were 
reported.  The  name  Spirocheta  pallidum  was  given  to  the  organism 
by  Schaudinn  upon  its  discovery.  Later  he  renamed  it  Treponema 
pallidum,  and  while  the  old  name  still  clings  to  it,  it  would  seem 
that  the  newer  appellation  is  the  more  correct. 

McDonagh,^  in  1913,  pubHshed  the  description  of  a  protozoon 
which  he  considers  the  true  causative  agent  of  syphilis,  and  later, 
in  1916,  in  an  exhaustive  treatise,  described  the  life  history  of  this 
organism  in  detail,  suggesting  the  name  Leucocytozoon  syphilidis. 
According  to  this  worker  the  Treponema  pallidum  represents  but  a 
part  of  the  life-cycle  of  the  protozoon,  developing  from  the  male 
gametocyte  and  later  fertilizes  the  female  gamete.  McDonagh 
states  that  Peri  Rocamora  and  Klausner  have  repeated  a  part  of 
his  work  and  substantiated  his  discoveries.  Other  confirmation 
apparently  is  lacking. 

The  place  in  biology  of  the  Treponema  pallidum  has  been  a 
moot  question  almost  from  its  discovery.  While  Schaudinn  did 
not  definitely  classify  the  organism,  his  writings  show  that  he  was 
inclined  to  consider  it  of  the  protozoa.  Some  observers  were  from 
the  first  very  insistent  that  the  Treponema  pallidum  is  a  bacterium, 
while  still  other  workers  assigned  to  it  a  place  midway  between 
the  bacterial  spiral  forms  and  the  flagellated  protozoa.^  It  seems 
to  the  author  that  this  is  but  an  evasion  of  the  question. 

The  argument  advanced  by  the  adherents  to  the  protozoal  nature 
of  the  treponema  are:  the  variations  in  thickness,  longitudinal, 
rather  than  transverse  division,  the  absence  of  cilia,  the  alleged 
presence  of  an  undulating  membrane;  and,  until  recently,  the  fact 
that  it  could  not  be  cultivated. 

Those  who  believed  that  the  organism  of  syphilis  is  a  true 
bacterium  deny  the  presence  of  an  undulating  membrane,  maintain 
that  cilia  are  observed,  that  transverse  division  occurs,  that  culti- 
vation may  be  effected  and  that  no  demonstrable  nucleus  and 
blepheroplast  exist.  Craig,-^  who  probably  has  done  as  much  work 
with  protozoa  in  general  and  the  Treponema  pallidum  in  particular 
as  any  man  in  America,  while  admitting  that  the  question  is  not 
definitely  settled,  is  of  the  opinion  that  this  organism  is  a  protozoon. 

The  well-known  effect  of  arsenic  upon  the  protozoa  and  the 
equally  well-known  efi^ect  of  salvarsan  upon  the  Treponema  pallidum 
seems  to  the  author  an  argument  in  favor  of  its  protozoal  nature. 

Morphology. — The  Treponema  pallidum  is  an  extremely  delicate 
organism,  4  to  14  microns  long,  by  about  \  micron  wide,  although 

1  The  Biology  and  Treatment  of  Venereal  Diseases,  Philadelphia  and  New  York, 
1916. 

2  KoUe  and  Hetsch:  Die  cxperimentelle  Bakt.,  Berlin,  1906.  Noguchi:  Personal 
Communication. 

3  Personal  communication. 

3 


34  ETIOLOGY 

occasionally  longer  individuals  are  seen,  even  up  to  40  microns  or 
more  in  length.  The  body  is  round  in  section,  not  flattened,  as 
is  the  case  with  some  spirochetes. 

Schaudinn^  described  flagella  at  either  end  of  the  organism,  but 
in  view  of  the  more  recent  work  on  the  subject  it  is  probable  that 
such  appendages  do  not  exist.  However,  at  the  beginning  of 
division,  two  very  fine  "cilia"  are  seen  at  one  end.  Schaudinn  de- 
scribed the  longitudinal  division,  stating  that  the  division  occurred 
in  a  very  few  seconds.  Other  investigators  claim  to  have  observed 
transverse  division,  but  Noguchi^  has  shown  that  in  cultures,  at 
least,  the  division  is  almost  constantly  longitudinal.  He  states 
that  during  division  the  curve  may  become  shallow,  but  that  after 
separation  is  complete  the  typical  curved  form  is  resumed.  Finally, 
he  states  that  the  process  is  not  rapid,  but  consumes  about  two 
hours  for  completion. 

The  organism  is  actively  motile,  the  motility  being  of  three 
varieties:  (1)  a  very  rapid,  smooth,  spinning  motion  on  its  long 
axis;  (2)  a  forward  and  backward  motion;  and  (3)  a  lateral,  bending 
motion.  The  typical  curves  persist  whether  the  organism  is  in 
motion  or  at  rest. 

Noguchi^  states  that  he  has  been  able  to  isolate  strains  of 
Treponema  pallidum  which  differ  in  morphology  and  pathogenicity, 
and  suggests  that  perhaps  these  dift'erences  may  account  for  certain 
clinical  variations  in  syphilis. 

Location  of  the  Treponema. — ^As  has  been  stated,  the  first  syphilitic 
lesion  to  give  up  the  secret  of  its  etiology  was  a  papule  of  the  vulva. 
Since  that  time  the  "pale  spirochete"  has  been  found  in  every  class 
of  syphilitic  lesion  and  in  all  organs  and  tissues  of  the  body.  It  has 
been  found  in  chancres,  in  syphilodermata,  in  gummata  and  condy- 
lomata, in  the  heart  and  bloodvessels,  in  the  liver,  spleen  and 
pancreas,  in  bones,  in  the  brain,  in  the  blood  and  lymph.  It  has 
even  been  found  in  the  urine*  and  spermatic  fluid^  of  men,  and  in  the 
milk  of  women.^ 

Animal  Inoculation. — That  syphilis  had  been  transmitted  to  the 
lower  animals  before  the  discovery  of  the  exciting  organism  was 
pointed  out  in  Chapter  I.  Metchnikoff  and  Roux,  Neisser  and 
others,  inoculated  the  higher  apes,  and  later  monkeys,  on  the  eye- 
brow with  material  obtained  from  the  superficial  lesions  of  syphilitics. 
This  produced  a  typical  lesion  at  the  site  of  inoculation  and  in  some 

1  Arb.  a.  d.  k.  Gsndhtsamte,  1907,  xxvi,  p.  17. 

2  Jour.  Exper.  Med.,  1911,  xvi,  p.  90. 

3  Jour.  Am.  Med.  Assn.,  1912,  Iviii,  p.  1164. 

"  Dreyer  and  Teuvel:  Brit.  Med.  Jour.,  May  12,  1906. 

5  Finger  and  Landsteiner:  SitzungsberichtQ  der  k.  Acad.  d.  Wissenchafern,  1905, 
Abtheil,  iii,  p.  497. 

6  Uhlenhuth  and  Mulzer:  Deutsch.  med.  Wchnschr.,  1912,  xxxix,  p.  891. 


MICROBIOLOGY  35 

cases  generalized  symptoms.  So,  soon  after  the  announcement  of  its 
discovery  by  Schaudinn,  numerous  investigators  attempted  to  detect 
the  treponema  in  the  lesions  of  these  animals,  and  almost  immedi- 
ately several  workers  announced  that  this  had  been  accomplished. 

Levaditi  and  Manouelian^  found  the  organism  in  the  lymphatic 
glands  of  a  monkey  with  syphilis  of  the  eyebrow,  while  Zabolotny^ 
found  it  in  the  spleen  of  a  syphilitic  monkey. 

At  first  it  was  thought  that  only  the  simians  were  susceptible 
to  syphilitic  infection,  but  it  was  soon  discovered  that  the  rabbit 
also  could  be  successfully  inoculated.'^  This  opened  up  a  wide  field 
for  experimental  investigation,  as  the  rabbit,  on  account  of  the  ease 
with  which  it  may  be  handled  and  its  inexpensiveness,  makes  an 
ideal  laboratory  animal.  At  first  the  anterior  chamber  and  cornea  of 
the  eye  were  inoculated,  but  later  the  testicle  and  scrotum  were  found 
to  develop  typical  lesions  after  injection  with  syphilitic  material. 

After  many  failures  Uhlenhuth  and  Mulzer^  succeeded  in  infecting 
young  rabbits  by  injecting  syphilitic  material  intracardially  which 
developed  into  general  infection,  and  after  passing  the  virus  through 
several  animals  were  able  to  infect  adult  rabbits,  producing  multiple 
lesions  of  the  skin,  mucous  membrane,  etc. 

In  inoculating  a  rabbit  intratesticularly  with  syphilitic  material 
from  a  chancre  a  preliminary  examination  is  made  with  the  dark 
field  illuminator^  to  determine  the  presence  of  the  treponemata. 
If  they  are  found  in  sufficient  numbers,  two  or  three  drops  of  serum 
are  taken  up  with  a  small  hypodermic  syringe,  and  after  shaving 
the  scrotum  of  a  large  rabbit  and  painting  with  iodin,  the  needle  is 
thrust  into  the  centre  of  the  testicle  and  the  serum  injected. 

After  about  two  weeks'  incubation  period  the  testicle  swells 
gradually,  and  at  the  same  time  the  consistency  becomes  increased, 
due  to  the  infiltration  of  cells.  The  maximum  growth  is  attained 
in  from  four  to  six  weeks,  at  which  time  immense  numbers  of  the 
treponemata  are  demonstrable.  In  order  to  transfer  the  infection 
from  one  rabbit  to  another  a  needle  is  thrust  into  a  testicular  nodule, 
a  few  drops  of  fluid  aspirated  and  injected  as  described  above. 

When  it  is  desired  to  use  a  mucous  patch  as  the  source  of  material 
a  small  cupper  is  applied  to  the  lesion  until  about  5  c.c.  of  serum  are 
obtained  which  are  injected  into  the  testicle. 

The  eye  is  inoculated  by  cocainizing  the  cornea,  making  a  short 
slit  and  inserting  a  small  piece  of  tissue  from  a  chancre  or  other 
infected  area.    Scrotal  lesions  are  produced  by  a  similar  technic. 

That  the  blood  of  syphilitics  from  the  chancre  to  the  terminal 
stages  of  general  paralysis  is  infectious  for  rabbits  has  been  shown 

1  Compt.  rend.  Soc.  de  biol.,  November  25,  1905;  February  10,  1906. 

^  Verhandlungen  der  Deutschen  dermatol.  Gesellschaft,  1907,  p.  304. 

3  Bertarelli:  Cent.  f.  Bak.  Orig.,  1906,  p.  320;  Parodi:  Ibid.,  1907,  p.  428. 

^  Deutsch.  med.  Wchnschr.,  1911,  xxxvii,  p.  51.  ^  See  Chapter  VII. 


36  ETIOLOGY 

by  a  number  of  investigators.  Hartwell^  reported  24  cases  of 
untreated  syphilis,  from  the  blood  of  which  he  inoculated  rabbits, 
securing  ten  positive  results.  Hartwell's  technic  was  to  draw  a  few 
cubic  centimeters  of  blood  from  a  superficial  vein  at  the  elbow,  and 
after  defibrination  to  inject  slowly  2  c.c.  into  the  testicles  of  rabbits. 

With  the  blood  of  general  paretics,  Graves^  has  succeeded  in 
successfully  inoculating  the  testicles  of  two  rabbits  with  syphilis. 

The  spinal  fluid  of  syphilitics  of  various  stages  has  served  as  a 
means  of  inoculating  animals  experimentally.  Hoffmann^  succeeded 
in  producing  a  characteristic  lesion  on  the  eyebrow  of  a  monkey 
by  inoculating  it  with  the  spinal  fluid  of  a  syphilitic  with  papular 
lesions.  Nichols  and  Hough*  successfully  inoculated  a  rabbit  intra- 
testicularly  with  the  spinal  fluid  of  a  patient  with  early  involvement 
of  the  central  nervous  system.  The  author,  following  their  technic 
in  3  cases  of  general  paralysis,  failed  to  produce  any  syphilitic  lesions. 

The  finding  of  the  Treponema  pallidum  in  the  stained  brain 
substance  of  paretics  and  in  the  spinal  cord  of  a  tabetic  by  Noguchi 
and  Moore^  stimulated  a  desire  on  the  part  of  numerous  investi- 
gators to  isolate  the  living  organism  from  these  structures.  Noguchi'' 
succeeded  in  doing  this  in  1  out  of  6  cases  by  emulsifying  small 
pieces  of  brain  tissue  removed  at  necropsy  soon  after  death,  and 
injecting  it  intratesticularly  into  rabbits.  Typical  syphilitic  nodules 
were  formed  in  two  rabbits,  although  the  incubation  period  was 
long,  and  many  treponemata  were  found  with  the  dark-field 
illumination  in  one  instance  and  by  the  Levanditi  method  of  staining 
in  the  other.  Nichols  and  Hough'^  reported  a  similar  apparently 
successful  inoculation  with  brain  substance  of  a  paretic  removed 
at  necropsy  one  hour  after  death.  In  their  experiments,  however, 
while  there  developed  fairly  characteristic  lesions,  they  were 
unable  to  demonstrate  treponemata  either  by  dark-field  illumina- 
tion or  by  the  Levaditi  method  of  staining. 

Wile^  was  able  to  produce  typical  syphilitic  lesions  in  the  testicles 
of  a  rabbit  by  inoculating  with  material  removed  from  the  brains 
of  paretics  during  life.  His  method  of  procedure  was  as  follows: 
6  typical  cases  of  general  paralysis  were  chosen,  and  after  painting 
the  site  with  iodin  and  anesthetizing  with  ethyl  chloride,  a  trephine 
hole  was  made  over  the  frontal  convolution  at  a  point  about  one- 
half  to  one  inch  from  the  midline  and  well  forward  of  the  course 
of  the  middle  meningeal  artery.  A  small  cylinder  of  brain  substance 
and  fluid  from  the  ventricle  were  removed  by  means  of  a  long,  thin 
trocar  needle  and  syringe  and  placed  in  a  sterile  Petri  dish  to  which 
had  been  added  a  small  amount  of  salt  solution.    In  the  material 

1  .Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  p.  142.  2  Ibid.,  1913,  Ixi,  p.  1504. 

'  Dermat.  Ztschr.,  1906,  xiii,  p.  561.  ^  Jour.  Am.  Med.  Assn.,  1913,  Ix,  p.  108. 

6  Jour.  Exper.  Med.,  1913.  xvii,  p.  232.  «  Jour.  Am.  Med.  Assn.,  1911,  ixi,  p.  85. 

'  Ibid.,  p.  120.  8  Jour.  Exper.  Med.,  1916,  xxiii,  p.  199. 


MICROBIOLOGY  37 

from  5  of  the  6  cases  treponemata  were  demonstrable  by  dark-field 
illumination,  in  that  of  one  of  the  cases  being  extremely  numerous. 
The  material  was  then  injected  into  the  testicles  of  a  large  rabbit. 
In  two  weeks  small  hard  nodules  could  be  felt  in  both  organs,  while 
in  four  weeks  large  numbers  of  actively  motile  organisms  were 
demonstrated  in  the  aspirated  fluid  from  the  nodules.  At  the  time 
of  writing  the  strain  had  been  cultivated  and  carried  through 
four  rabbits,  seemingly  increasing  in  virulence. 

Nichols^  has  shown  that  the  strain  of  pallida  isolated  by  him 
and  Hough  from  the  spinal  fluid  showed  marked  peculiarities ;  that 
the  organisms  were  of  thick  form,  resembling  the  thick  form 
described  by  Noguchi;  that  they  produced  hard,  well-demarcated 
lesions  with  necrotic  centres ;  that  there  was  a  characteristic  location 
of  the  lesions;  that  the  incubation  period  was  short;  and  that  a 
tendency  to  generalize,  with  lesions  of  the  skin  and  eye  following 
local  inoculation  of  the  testicle  and  scrotum,  was  noted.  The  same 
morphological  characteristics  are  described  by  Wile  in  his  original 
communication  concerning  the  strain  isolated  by  him  from  paretics. 
In  a  later  paper,^  however,  he  states  that  such  characteristics  are 
not  observed  in  cultures. 

From,  these  findings  and  from  certain  clinical  data,  Nichols  suggests 
as  did  Noguchi,  that  there  may  be  strains  of  Treponema  pallidum 
which  have  certain  definite  predilections  for  certain  tissues.  In 
this  connection  it  may  be  noted  that  Richard  Carmicheal  (1779- 
1849),  at  a  very  early  date,  was  of  the  opinion  that  not  only  did  one 
virus  of  syphilis  exist,  but  that  there  were  a  great  number,  varying 
according  to  the  lesions  the}'  produced. 

Agglutination. — Ivolmer^  states  that  agglutination  of  Treponema 
pallidum  does  not  occur  with  normal  human  or  rabbit  blood  in 
dilution  as  low  as  1  to  20,  nor  with  the  blood  of  individuals  in  the 
active  stages  of  syphilis.  However,  agglutinins  for  Treponema 
pallidum  are  rapidly  produced  in  young  rabbits  upon  injection  with 
living  organisms.  Zinnser  and  Hopkins*  have  shown  that  normal 
rabbit  and  human  sera  possess  slight  agglutinating  properties  for 
cultural  pallida,  that  the  sera  of  certain  syphilitic  individuals  possess 
these  properties  and  that  rabbits  injected  with  cultures  of  the 
organisms  possess  them  in  a  marked  degree.  These  authors  state 
that  no  quantitative  difference  of  diagnostic  value  between  the 
sera  of  normal  individuals  and  those  of  syphilitics  has  been 
demonstrated. 

In  a  subsequent  paper,  Zinnser,  Hopkins  and  McBurney,^  point 
out  that  while  antibodies  may  be  produced  in  rabbits  by  injecting 

1  Jour.  Exper.  Med.,  1914,  xix.  p.  362. 

2  Wile:  Jour.  Am.  Med.  Assn.,  1916,  Ixvi,  p.  646. 

3  Jour.  Exper.  Med.,  1913,  xviii,  p.  109. 

^  Ibid.,  1915,  xxi,  p.  576.  «  jbid.,  1916,  xxxiii,  p.  341. 


38 


ETIOLOGY 


with  cultural  organisms,  which  agglutinate  these  organisms,  that 
they  possess  practially  no  agglutinating  properties  for  virulent 
treponemata  obtained  directly  from  lesions. 

Cultivation. — Following  the  discovery  of  the  Treponema  pallidum 
the  natural  sequence  was  its  attempted  cultivation.  Numerous 
investigators  worked  toward  this  end,  but  it  was  not  until  1909 
that  Schereschewsky^  was  able  to  show  multiplication  of  the 
organism  in  gelatinized  horse  serum  by  planting  deeply  in  this 
medium  pieces  of  tissue  from  human  syphilitic  lesions.  At  this 
time  he  was  not  able  to  obtain  pure  cultures,  but  subsequently 
reported  the  successful  accomplishment  of  this 
feat  by  planting  anaseptically  excised  sj^phil- 
itic  papule.^  Following  Schreschewsky's 
technic,  Muhlen''  and  later  Hoffmann^  suc- 
ceeded in  obtaining  cultures  of  treponemata 
which  they  were  able  to  purify  by  the  use 
of  Muhlen's  horse-serum  agar. 

While  it  is  probable  that  the  above-men- 
tioned workers  succeeded  in  cultivating  the 
Treponema  pallidum,  their  technic  lacked  re- 
finement and  their  cultures  were  not  patho- 
genic. However,  the  researches  of  Noguchi^ 
culminated  in  1912  in  success,  and  we  are 
now  able  to  cultivate  the  Treponema  pallidum 
direct  from  the  lesion  in  the  human  syphilitic, 
to  transmit  the  disease  to  the  lower  animals 
by  inoculation  with  the  cultures,  and  to  recover 
the  organism  in  pure  culture  from  the  lesions 
produced.  Thus  the  requirements  of  Koch's 
law  have  been  fulfilled  and  one  battle  in  the 
long  war  against  syphilis  has  been  won. 

Two  conditions  for  the  direct  cultivation 
of  the  treponemata  are  pointed  out  by 
Noguchi  to  be  of  the  utmost  importance: 
(1)  absolute  anaerobiosis,  and  (2),  the  prop- 
erty of  the  organism  of  migrating. 
The  medium  used  in  a  solid  one,  consisting  of  two  parts  of  a 
slightly  alkaline  2  per  cent,  agar  and  one  part  of  ascitic  fluid. 
Large  test-tubes  are  used  (2  by  20  cm.),  15  c.c.  of  the  medium  are 
placed  in  each  tube,  and.  in  the  bottom  of  the  tube  is  placed  a  small 
piece  of  sterile  rabbit  kidney  or  testicle.  Each  organ  will  furnish 
enough  tissue  for  about  one  dozen  tubes.    The  object  of  the  tissue 

1  Deutsch.  med.  Wchnschr.,  1909,  xxxv,  p.  835. 

2  Schereschewsky:  Ibid.,  1915.  xxxix,  p.  1420.  ^  Ibid.,  1909,  xxxv,  p.  1261. 
^  Ztschr.,  Hyg.  v.  Infectionskrankh.,  1911,  Ixviii,  p.  27. 

6  Jour.  Exper.  Med.,  1912,  xvi,  p.  90. 


Fig.  1. — Pure  culture 
of  Treponema  pallida. 
Noguchi's  method. 


MICROBIOLOGY  39 

is  to  remove  slight  traces  of  oxygen,  and  probably,  also,  to  furnish 
a  special  kind  of  nutriment.  In  preparing  the  medium  the  tissue 
is  first  placed  in  the  bottom  of  the  tube  and  the  melted  agar  at 
45°  to  50°  C.  and  the  ascitic  fluid  are  added  in  the  proper  proportions. 
When  the  medium  has  solidified,  a  layer  of  sterile  paraffin  oil  is 
added  to  prevent  evaporation.  The  tubes  should  be  incubated  for 
several  days  to  determine  their  sterility. 

The  inoculation  is  made  by  snipping  off  suitable  pieces  of  chancre, 
condyloma,  or  papule  after  first  cleansing  with  sterile  salt  solution. 
The  pieces  are  immediately  placed  in  sterile  salt  solution  to  which 
has  been  added  1  per  cent,  sodium  citrate.  The  pieces  are  cut  into 
very  small  fragments.  One  piece  is  emulsified  in  a  mortar  and 
examined  with  the  dark-field  illuminator  for  the  presence  of  the 
treponemata.  If  the  organisms  are  shown  to  be  present  in  sufficient 
numbers,  a  small  piece  is  placed  in  a  tube  of  the  medium  by  forcing 
it  to  the  bottom  of  the  tube  with  a  small  glass  rod.  A  few  drops 
of  the  emulsified  tissue  are  also  "planted"  deeply  in  the  medium 
by  means  of  a  capillary  pipette.  It  is  desirable  to  inoculate  several 
tubes.  They  are  now  incubated  at  a  constant  temperature  of 
37°  C.  for  two  or  three  weeks. 

On  account  of  the  contamination  of  the  tissue  with  bacteria 
there  is  usually  a  dense  growth  along  the  stab  canal.  The  rest  of 
the  medium  takes  on  a  milky  appearance,  due  to  the  growth  of  the 
treponemata  and  bacteria.  If  a  capillary  pipette  is  introduced 
into  the  medium  and  some  of  the  contents  withdrawn,  if  there  has 
been  growth  of  the  organisms  they  may  be  detected  with  the  dark- 
field  illuminator.  Owing  to  the  presence  of  putrefactive  bacteria 
there  is  a  foul  odor  to  the  tubes,  and  purification  is  accomplished 
by  transplanting  with  the  capillary  pipette  some  of  the  growth 
to  fresh  media.  After  a  sufficiently  long  incubation  (two  or  three 
weeks)  there  will  be  a  hazy  appearance  radiating  from  the  stab 
canal  toward  the  sides  of  the  tube.  A  second  transfer  is  made,  and 
after  a  sufficient  growth  is  observed  the  tube  is  marked  about  the 
middle  with  a  diamond  pencil  or  file  and  a  red-hot  pointed  glass 
rod  applied  to  the  cut.  When  the  tube  cracks,  the  upper  part  being 
removed,  the  surface  of  the  agar  thus  exposed  is  sterilized  with 
alcohol.  The  agar  is  now  broken  transversely,  leaving  a  clear  surface 
on  which  the  growth  of  treponemata  is  readily  seen.  The  growth  is 
taken  up  with  a  capillary  pipette  without  touching  the  stab  canal  for 
dark-field  examination  and  reinoculation.  It  is  sometimes  neces- 
sary to  make  several  transplants  before  a  pure  culture  is  obtained. 

An  easier  and  more  simple  method  of  obtaining  a  pure  culture 
of  Treponema  pallidum  was  first  described  by  Noguchi.^  It  consists 
of  inoculating  a  rabbit  intratesticularly,  and  after  a  well-marked 

1  Jour.  Exper.  Med.,  1911,  xiv,  p.  99. 


40  ETIOLOGY 

syphilitic  nodule  has  developed  to  excise  the  testicle.  After  dark- 
field  examination  of  the  nodule  has  determined  the  presence  of  a 
large  number  of  organisms  it  is  planted  in  the  ascitic  fluid  agar 
as  described  above  for  the  direct  cultivation.  The  advantage  of 
this  method  is  that  the  testicular  lesion  in  the  rabbit  is  much 
freer  of  contaminating  organisms  than  are  the  lesions  in  the  human 
subject. 

Zinsser,  Hopkins,  and  Gilbert^  have  reported  the  successful 
cultivation  of  Treponema  pallidum  on  various  media  without  the 
addition  of  fresh  tissue.  Thus  they  were  able  to  obtain  excellent 
growth  in  slightly  acid  broth  and  sheep  serum  with  autoclaved 
tissue  (kidney,  liver,  brain,  lung,  heart),  and  good  growth  with 
simple  meat  juice,  autoclaved.,  without  the  removal  of  the  clots. 
They  also  obtained  growth  of  the  pallida  in  ascitic  fluid  agar  in 
symbiosis  with  various  bacteria,  the  best  with  streptococcus.  They, 
further,  have  been  able  to  secure  more  luxuriant  growths  that  have 
been  produced  heretofore. 

The  standards  laid  down  by  Noguchi^  for  the  identification  of 
the  Treponema  pallidum  in  pure  culture  are:  (1)  correct  mor- 
phology; (2)  necessity  of  the  presence  of  fresh  sterile  tissue  in 
culture  medium;  (3)  strict  anaerobiosis;  (4)  rather  faint  hazy 
growth  in  solid  or  fluid  mediums  without  any  noticeable  change 
in  the  proteid  constituents;  (5)  non-production  of  any  oft'ensive 
odor  in  culture;  (6)  capability  of  inciting  an  allergic  reaction  on 
the  skin  of  certain  cases  of  syphilis  and  parasyphilis  (so-called  luetin 
reaction);  (7)  specific  complement-fixation  with  the  antipallida 
immune  serum  or  certain  serums  from  human  cases  of  syphilis, 
provided  that  the  antigen  is  suspended  in  saline  solution  and  not 
prepared  by  alcoholic  extraction;  and  (8)  pathogenicity.  The 
pathogenicity  may  be  gradually  attenuated  in  course  of  cultivation, 
but  the  other  seven  conditions  should  be  constantly  fulfilled. 

MODES  OF  TRANSMISSION. 

Now  that  the  Treponema  pallidum  has  been  proved  beyond  the 
shadow  of  a  doubt  to  be  the  infective  agent  in  syphilis,  the  modes  of 
transmission  of  the  disease  are  better  understood.  It  is  at  the 
present  time  almost  universally  accepted  that  in  order  that  the 
treponema  may  gain  access  to  the  body,  there  must  be  a  solution  of 
the  continuity  of  the  epithelium. 

There  are  three  methods  by  which  syphilis  may  be  contracted, 
viz.,  by  direct  contact,  by  intermediate  contact  and  congenitally. 

Direct  Contact. — By  far  the  greatest  number  of  cases  of  syphilis 
are  acquired  by  direct  contact,  and  of  these  the  vast  majority 

1  Jour.  Exper.  Med.,  1915,  xxi,  p.  213. 

2  Jour.  Am.  Med.  Assn.,  1912,  lix,  p.  1236. 


MODES  OF   TRANSMISSION  41 

are  by  direct  contact  during  the  sexual  act.  This  is  probably 
partly  accounted  for  by  the  fact  that  the  skin  and  mucous  membrane 
of  the  parts  involved  are  very  delicate,  and  that  slight  abrasions 
are  liable  to  occur.  Other  locations  than  the  genitalia,  such  as  the 
lips,  tongue,  tonsils,  anus,  etc.,  are  occasionally  the  seat  of  syphilitic 
infection  through  unnatural  sexual  practices. 

Besides  the  acquiring  of  syphilis  through  sexual  acts  it  not 
infrequently  is  disseminated  through  kissing.  Not  only  is  this 
true  of  the  kissing  of  the  roue,  but  often  the  disease  is  spread  in 
ordinary  family  life,  and  even  to  young  children  in  this  manner. 

Shamberg^  reports  a  most  distressing  epidemic  of  8  cases  of 
syphilis  transmitted  through  kissing.  The  infections  occurred  at  a 
party  where  juvenile  kissing  games  were  indulged  in,  and  were 
disseminated  by  a  young  man  with  a  chancre  of  the  lip.  Seven 
young  women  and  a  second  young  man  developed  labial  chancres. 
The  latter  probably  was  infected  by  organisms  from  the  lips  of  one 
of  the  young  women,  as  he  did  not  come  in  contact  with  the  original 
offender. 

Sucking  is  the  source  of  a  certain  number  of  infections,  although 
this  was  the  case  more  when  the  professional  breast  drawer  plied 
his  trade.  The  practice  of  sucking  the  penis  to  stop  the  flow  of 
blood  following  ritual  circumcision  has  been  known  to  spread 
syphilitic  infection. 

Manual  and  corporeal  contact  come  in  for  their  share  in  the 
spreading  of  the  Treponema  pallidum.  The  practice  of  amorously 
dallying  with  the  genital  organs  has  resulted  in  inoculations,  and 
a  case  of  chancre  of  the  great  toe  due  to  contact  with  the  female 
genitalia  is  recorded. 

Many  physicians  have  become  infected  with  syphilis  during 
examinations  and  operations  on  syphilitics,  and  even  at  necropsies. 
The  author  has  seen  a  number  of  such  cases.  That  syphilis  may  be 
acquired  by  corporeal  contact,  as  during  sleep  or  by  carrying 
syphilitics,  is  beyond  doubt.  No  case  of  laboratory  infection  through 
handling  cultures  of  Treponema  pallidum  has  been  recorded,  but 
such  an  occurrence  is  well  within  the  range  of  possibility. 

Intermediate  Contact. — By  intermediate  contact  is  meant  the 
interposition  of  some  object  between  the  recipient  of  the  infection 
and  the  source  of  the  same.  These  objects  are  numberless,  and  to 
make  even  an  approximate  list  would  be  impossible.  Probably  the 
most  important  of  these  is  the  common  face  towel,  as  Zinnser  and 
Hopkins^  have  shown  the  organism  of  syphilis  may  live  for  at  least 
eleven  and  one-half  hours  under  conditions  that  simulate  those 
found  on  the  towel.    Drinking  cups  and  glasses,  even  the  sacred  com- 

1  Jour.  Am.  Med.  Assn.,  1911,  Ivii,  p.  783. 

2  Ibid.,  1914,  Ixii,  p.  1802. 


42  ETIOLOGY 

munion  cup,  have  been  the  means  of  spreading  syphilitic  infection. 
However,  according  to  the  above-mentioned  authors,  the  treponema 
does  not  hve  longer  than  one  hour  on  glass.  The  seats  of  public 
toilets  have  been  charged  with  frequently  conveying  syphilitic 
infection,  but  probably  are  not  of  as  much  importance  in  this 
respect  as  they  once  were  considered.  Any  other  object  which  may 
come  in  contact  with  lesions  of  a  syphilitic  and  with  the  abraded 
epithelial  surface  of  a  non-syphilitic  may  convey  the  infection. 

One  of  the  most  extraordinary  cases  of  infection  by  intermediate 
contact  recently  was  called  to  the  attention  of  the  author.  A  man 
in  passing  along  the  street  was  accidentally  struck  on  the  nose 
by  a  whip  lash  in  the  hands  of  a  teamster,  and  a  §mall  abrasion 
created  which  healed  in  a  very  few  days.  Some  time  later  a  chancre 
developed  at  the  site  of  the  injury,  and  upon  investigation  it  was 
learned  that  the  teamster  was  suffering  from  syphilitic  lesions  of  the 
mouth  and  was  in  the  habit  of  moistening  the  cracker  of  his  whip 
with  saliva. 

SECONDARY  ETIOLOGICAL  FACTORS. 

While,  as  has  been  shown,  the  Treponema  pallidum  is  the  infecting 
agent  in  syphilis  there  are  certain  secondary  etiological  factors 
which  must  be  considered. 

Idiosyncrasy.— Immunity. — That  some  individuals  are  less  suscep- 
tible than  others  to  infectious  diseases  in  general,  and  to  syphilis 
in  particular,  is  undoubted.  That  this  is  not  due  to  the  presence  of 
specific  antibodies  on  the  one  hand,  but  to  the  lack  of  resistance, 
inherited,  or  due  to  debilitating  conditions,  or  perhaps  to  both, 
on  the  other,  has  been  proved.  It  is  a  well-known  fact  that  several 
men  may  have  relations  with  a  luetic  woman  and  perhaps  only 
one  contract  the  disease.  Of  course,  if  we  accept  the  theory  that 
there  must  be  a  break  in  the  continuity  of  the  integument  for 
infection  this  observation  may  be  accounted  for. 

Such  a  condition  as  absolute  immunity  probably  does  not  exist 
in  regard  to  any  infectious  disease.  That  is,  if  a  sufficiently  large 
number  of  the  infective  organisms  are  inoculated  into  the  individual 
he  will  contract  the  disease,  no  matter  what  his  resistive  powers 
may  be. 

Until  recently  it  was  thought  that  one  attack  of  syphilis  protected 
the  person  from  a  second  attack,  although  a  few  cases  of  second 
attacks  had  been  observed.  But  since  the  more  modern  methods 
of  diagnosis  and  treatment  have  been  evolved  second  attacks  have 
been  more  frequent,  and  even  third  attacks  have  been  reported. 

Colles'  Law.- — Colles'  law,  named  after  Abraham  Colles  (1773- 
1843),  the  celebrated  Irish  surgeon,  who  established  it  in  1837, 
stated  that  the  mother  of  a  syphilitic  child  could  not  become 


SECONDARY  ETIOLOGICAL  FACTORS  43 

infected  with  the  disease,  that  is,  that  she  was  immune.  This 
later  was  described  as  being  due  to  antibodies  reaching  her  from  the 
child  through  the  placenta.  This  law  has  been  disproved  (1)  by 
showing  paternal  congenital  syphilis  is  impossible,  and  (2)  that  the 
mother  already  has  syphilis.  Profeta's  law  held  that  a  healthy 
child  could  not  become  infected  by  a  syphilitic  mother,  in  other 
words,  it  was  immune,  and  that  the  immunity  was  acquired  from 
the  mother  through  the  placental  circulation.  This  law,  too,  has 
been  disproved.  It  is  now  recognized  that  no  immunity  to  syphilis 
exists;  that  so  long  as  Treponema  pallida  remain  in  the  body 
no  superinfection  can  occur,  but  that  as  soon  as  the  organisms  have 
all  been  destroyed  the  body  is  open  to  reinfection. 

Age. — No  period  of  life  is  proof  against  the  ravages  of  this  most 
ubiquitous  of  diseases.  Old  age  may  contract  it  in  the  tottering 
years  of  its  decline;  youth,  proud  in  its  strength,  may  fall  a  victim, 
while  the  babe  yet  unborn  may  become  infected.  Of  course,  it  is 
in  the  years  following  puberty  and  before  "the  grinders  have  ceased 
because  they  are  few,"  that  syphilis  is  most  likely  to  be  contracted. 
Wolbarst^  reports  a  chancre  of  the  lower  abdominal  wall  in  a  boy, 
aged  two  years,  while  syphilis  insontium  is  far  from  unknown  in 
the  very  old.  Syphilis  contracted  during  sexual  intercourse  has 
been  observed  at  the  extremes  of  life.  Wolbarst^  saw  a  genital 
chancre  in  a  boy,  aged  five  years,  while  the  author  saw  a  similar 
lesion  in  a  negro  boy,  aged  six  years,  who  said  he  had  had  intercourse 
with  his  sister.  At  the  other  extreme  the  author  saw  a  chancre  of 
the  penis  of  a  white  man,  aged  sixty-six  years. 

That  young  children  sometimes  are  exposed  to  syphilitic  infection 
of  the  genitals  is  due  to  the  superstition  still  prevalent  among 
certain  classes  that  intercourse  with  a  virgin  will  cure  venereal 
disease. 

Syphilis  in  the  very  young  or  in  the  very  old  is  usually  more 
severe  than  others,  although  it  may  run  a  mild  course  at  any  age. 

Sex. — That  syphilis  should  be  more  common  in  men  than  m 
women  is  almost  self-evident.  The  social  law  which  throws  a  cloak 
about  the  chastity  of  women  in  the  home  and  permits  with  little  or 
nothing  more  than  a  shrug  the  "sowing  of  wild  oats"  by  men  is  in 
itself  enough  to  cause  the  number  of  syphilitic  men  to  exceed  the 
number  of  women  contracting  the  disease.  Then,  too,  the  fact  that 
women  remain  more  in  the  home  keep  them  safer  from  extragenital 
infection  from  drinking  cups,  public  toilets,  etc. 

However,  Hubert^  found  of  8652  patients  at  the  first  medical 
clinic  of  Munich  on  whom  Wassermann  tests  were  performed  that 

1  Transactions  of  the  Fifteenth  International  Congress  on  Hygiene  and  Demog- 
raphy, held  at  Washington,  D.  C,  September  23-28,  1912. 

2  Ibid. 

'Miinch.  med.  Wchnschr.,  1915,  Ixii,  p.  1314. 


44  ETIOLOGY 

759,  or  8.8  per  cent.,  were  positive.  Of  the  8652  patients,  4739 
were  men  and  3903  were  women.  Of  the  men  405,  or  8.5  per  cent., 
were  found  to  be  syphilitic,  while  of  the  women  354,  or  9  per  cent., 
were  found  infected. 

It  has  been  stated  that  syphilis  in  women  is  more  severe  than 
in  men,  but  Keyes^  has  pointed  out  that  this  is  not  the  case,  except 
that  there  may  be  more  profound  toxemia  in  women. 

It  is,  however,  a  matter  of  common  observance  that  the  late 
nervous  manifestations  of  syphilis,  tabes,  and  paresis  are  of  com- 
paratively rare  occurrance  in  women.  Montgomery^  has  offered 
the  following  as  a  possible  explanation  of  this: 

1.  The  thyroid  is  more  active  in  females  than  in  males,  as  shown 
by  the  frequency  of  its  enlargement  in  females,  and  by  the  much 
greater  number  of  cases  of  Basedow's  disease  in  females  than  in 
males. 

2.  A  principal  constituent  of  thyroid  secretion  is  iodothyrin. 

3.  All  the  iodin  compounds  exert  a  marked  influence  on  syphilis. 

4.  The  influence  of  iodothyrin,  although  small,  would  be  exerted 
continuously  and  for  a  long  time,  and  it  must  be  remembered  that 
some  of  the  greatest  phenomena  in  nature  are  produced  by  small 
causes  acting  through  a  long  time. 

5.  The  course  of  syphilis,  and  especially  of  neural  syphilis,  is 
very  different  in  men  and  in  women,  and  this  difference  may  be  due 
to  the  greater  activity  of  the  thyroid  in  women,  especially  so  modify- 
ing the  virus  that  it  does  not  affect  the  nervous  system. 

Race. — It  has  long  been  considered  that  race  has  an  important 
bearing  on  syphilis,  that  certain  peoples  show  more  resistance  to 
the  disease  than  others,  and  that  in  certain  races  the  manifestations 
are  more  severe.  That  syphilis  is  more  frequent  among  the  American 
negroes  than  among  whites  has  been  shown  statistically  by  numbers 
of  writers.  In  2200  cases  of  skin  disease  among  negroes,^  Fox 
found  596  cases  of  syphilis,  while  in  an  equal  number  of  whites 
there  were  but  279  syphilitics. 

Vedder^  has  shown  that  among  the  colored  enlisted  men  of  the 
army  36  per  cent,  were  probably  syphilitic,  while  among  the  white 
enlisted  men  only  16.08  per  cent,  were  infected. 

The  author  is  of  the  opinion  that  this  state  of  affairs  is  not  due  to  a 
greater  susceptibility  on  the  part  of  the  negro  but  to  his  almost 
absolute  lack  of  morality  and  cleanliness. 

In  regard  to  a  greater  virulence  of  the  disease  in  certain  races  the 

1  Syphilis,  New  York  and  London,  1908,  p.  45. 

2  Med.  Rec,  1915,  Ixxxviii,  p.  820. 

'  Jour.  Cutan.  Dis.,  1911,  xxvi,  p.  67. 

<  The  Prevalence  of  Syphilis  in  the  Army,  Bulletin  No.  8,  War  Department,  Office 
of  the  Surgeon  General,  Washington,   1915. 


SECONDARY  ETIOLOGICAL  FACTORS  45 

author  can  find  no  convincing  evidence.  It  has  been  stated  that 
in  the  negro  syphiHs  is  less  severe  than  in  the  white.  The  author  in 
dealing  with  quite  a  large  number  of  negro  syphilitics  in  the  South 
has  formed  the  opinion  that  this  is  ndt  the  case,  that  the  disease 
shows  about  equal  severity  in  the  two  races,  except  that  the  negro 
seems  to  be  less  prone  to  develop  syphilis  of  the  nervous  system. 
It  is  true,  however,  that  certain  cutaneous  manifestations  are  more 
often  found  in  the  negro;  for  example,  the  annular  papular  syphilo- 
derm  is  quite  frequent  in  this  race  and  is  very  rare  in  the  white. 

Climate. — Climate  appears  to  have  very  little  influence  on  the 
course  of  syphilis.  It  has  been  claimed  that  in  the  extremely  hot 
and  extremely  cold  countries  syphilis  is  more  malignant  than  in  the 
temperate  regions.  It  is  possible  that  the  cutaneous  lesions  are 
more  pronounced  in  hot  countries.  It  would  appear,  however, 
that  the  main  factor  to  be  considered  is  whether  or  not  the  victim 
of  syphilis  has  become  acclimated  to  the  region  in  which  he  is 
residing  at  the  time  he  is  suffering  with  the  disease.  In  other  words, 
in  a  native  of  a  torrid  or  frigid  zone  contracting  syphilis  soon  after 
his  arrival  in  a  temperate  region  the  disease  would  possibly  run 
a  more  severe  course  than  it  would  had  he  contracted  the  disease 
and  remained  in  his  native  land. 

Occupation. — That  the  occupation  of  an  individual  may  be  the 
means  of  him  contracting  syphilis  is  probably  not  taken  into 
account  by  many  in  choosing  a  vocation.  The  importance  of 
occupation  in  contracting  genital  syphilis  or  syphilis  through  the 
sexual  act  enters  into  the  lives  of  but  very  few.  Prostitutes  and 
certain  low  individuals  who  give  themselves  up  to  unnatural  sexual 
acts  (if  such  may  be  said  to  have  an  occupation)  are  more  liable  to 
syphilitic  infection  than  those  who  live  moral  lives. 

However,  syphilis  insonitinn  perhaps  not  infrequently  is  con- 
tracted by  intermediate  contact  by  glass-blowers,  musicians  (by 
two  men  playing  on  the  same  wind  instrument),  laundresses  (by 
handling  soiled  clothing),  and  by  many  others. 

Civil  State. — It  is  quite  evident  that  in  men  the  unmarried  are 
more  exposed  to  syphilitic  infection  than  the  married,  and  that  in 
women  the  reverse  is  true,  since  a  large  percentage  of  women  con- 
tracting syphilis  do  so  from  their  husbands.  Of  course,  there  are 
many  exceptions  to  this  rule,  and  we  find  syphilis  in  a  large  number 
of  unmarried  prostitutes  and  in  married  men  of  vicious  habits, 
while  the  civil  state  would  seem  to  have  no  bearing  on  extragenital 
infection.  Divorcees  of  both  sexes  are  perhaps  more  frequently 
infected  with  syphilis  than  individuals  of  other  civil  states. 

Social  Condition. — Civilization. — Syphilis  is  no  respecter  of  persons. 
It  attacks  the  king  in  his  castle  and  the  beggar  at  his  gate.  How- 
ever, those  low  in  the  social  scale  are  more  prone  to  indulge  in 


46  ETIOLOGY 

sexual  excesses,  owing  to  the  conditions  of  housing,  etc.,  than  those 
of  high  degree,  and,  further,  they  do  not  as  often  employ  prophy- 
lactic measures,  so  contract  syphilis  more  frequently. 

Among  most  savage  people  promiscuous  sexual  intercourse  is  the 
rule,  therefore  it  is  natural  to  expect  that  the  infection  of  one 
individual  with  syphilis  would  mean  the  rapid  spread  of  the  disease. 
This  is  indeed  the  case,  and  we  find  many  instances  of  almost  entire 
tribes  becoming  luetic  in  an  incredibly  short  time. 


CHAPTER  IV. 
PATHOLOGY. 

In  brief  the  pathology  of  syphilis  may  be  said  to  consist  of  the 
reaction  of  the  tissues  to  the  invading  treponemata,  and  the  general 
picture  is  the  same  no  matter  what  portion  of  the  body  is  affected. 
There  is  proliferation  of  the  fixed  connective-tissue  elements, 
infiltration  of  round  and  plasma  cells  and  the  formation  of  more  or 
less  circumscribed  granulomata  with  or  without  giant  cells.  No 
organ  or  tissue  is  exempt  from  invasion,  although  as  pointed  out 
in  the  chapter  on  Etiology  there  seems  to  be  some  evidence  to 
substantiate  the  theory  that  different  strains  of  treponemata 
exist  with  greater  affinity  for  certain  tissues  than  for  others.  The 
isolating  of  similar  short,  thick  organisms  by  both  Nichols  and 
Wile  from  cases  of  syphilitic  involvement  of  the  nervous'^system, 
and  the  well-established  clinical  fact  that  individuals  who  have  but 
slight  skin  manifestations  frequently  later  develop  syphilis  of  the 
nervous  system,  certainly  are  suggestive.  The  bloodvessels  play 
a  most  important  part  in  the  pathology  of  syphilis  and  are  found 
almost  from  the  first  to  be  the  seat  of  endarteritis  and  inflammatory 
infiltration. 

For  reasons  stated  in  the  chapter  on  Clinical  History  it  seems 
best  to  discard  the  stages  of  Ricord  and  to  classify  the  various 
manifestations  of  syphilis  upon  anatomical  and  clinical  grounds. 
Therefore  in  discussing  the  pathology  of  syphilis  the  various  lesions 
will  be  described  from  an  anatomical  standpoint,  although  for 
convenience  they  will  be  discussed  in  the  sequence  in  which  they 
usually  appear. 

Visceral  pathology  and  the  pathology  of  the  osseous,  muscular 
and  nervous  systems  will  be  discussed  in  Part  II. 

CHANCRE. 

The  gross  appearance  of  the  chancre,  which  usually  is  the  first 
manifestation  of  acquired  syphilis  and  which  is  in  reality  a  clinical 
symptom,  varies  greatly  in  size,  shape  and  location  and  will  be 
described  fully  in  the  chapter  on  Clinical  History. 

Histopathology. — The  epidermis  is  nearly  always  the  first  tissue 
to  be  affected  by  the  invading  organisms.    Here  they  lodge  in  the 


48  PATHOLOGY 

interephithelial  lymph  spaces.  Soon  they  proceed  to  the  peri- 
vascular lymph  spaces  and  bloodvessels  of  the  corium  where  they 
multiply  rapidly.  Regardless  of  the  large  number  of  treponemata 
usually  present  the  tissues  are  little  damaged.  Only  an  occasional 
cell  is  destroyed  and  absorbed.  There  is  very  early  the  formation 
of  new  capillaries  and  a  marked  infiltration  of  lymphocytes  and 
plasma  cells  and  a  slight  infiltration  of  endothelial  leukocytes.  This 
infiltration  affects  mainly  the  periphery  of  the  chancre  and  the 
walls  of  the  bloodvessels.  Polymorphonuclear  leukocytes  may  be 
present  in  considerable  numbers,  or  they  may  be  entirely  absent. 
Eosinophiles  are  occasionally  seen. 

The  outline  of  the  process  is  sharply  defined  in  the  beginning 
but  later  becomes  more  diffuse.  The  newly  formed  capillaries 
as  well  as  the  old  ones  suffer  from  swelling  and  proliferation  of 
the  endothelium  which  narrows  and  sometimes  occludes  the  lumen. 
Giant  cells,  which  are  rather  common  in  some  other  syphilitic 
lesions,  are  rare  in  chancres.  The  induration  is  mainly  due  to  a 
regenerative  proliferation  of  fibroblasts,  rather  than  to  infiltration 
of  leukocytes.  The  epidermis  becomes  either  atrophied  or  hyper- 
trophied,  or  erosion  or  ulceration  may  take  place. 

Lymphatic  Glands. — The  enlargement  of  the  lymphatic  glands 
adjacent  to  the  chancre  is  the  earliest  symptom,  showing  that  the 
infecting  organisms  have  left  the  portal  of  entry.  At  this  time  the 
glands  usually  show  nothing  microscopically  but  hyperplasia  of  the 
lymphocytes  with  many  treponemata. 

Later  in  the  course  of  the  disease  there  usually  is  an  enlargement 
of  certain  groups  of  glands  marked  by  more  or  less  infiltration 
of  small  round  cells  in  the  follicles  and  lymph  sinuses,  with  usually 
an  increase  in  the  connective  tissue  in  the  capsule  and  trabeculse. 
The  reticular  tissue  may  be  thickened  and  infiltration  of  the  walls 
of  the  bloodvessels  is  usually  observed.  Treponemata  may  also  be 
demonstrated. 

The  lymphatic  glands  may  rarely  be  the  seat  of  the  so-called 
gummatous  formation  which  is  very  different  Jrom  the  above- 
described  adenitis.  There  is  a  marked  circumscribed  infiltration  of 
plasma  cells  and  lymphocytes  with  thickening  of  the  walls  of  the 
bloodvessels  while  in  the  larger  gummata  the  central  portion 
becomes  caseous  and  necrotic. 

Amyloid  degeneration  of  the  lymphatic  glands  also  may  occur. 

Cutaneous  Lesions. — It  is  not  strange  that  lesions  which  exhibit 
so  many  and  diverse  forms  as  the  cutaneous  manifestations  of 
syphilis  should  present  difficulties  of  description  and  classification. 
While  the  all-important  point  for  consideration  of  a  pathological 
cutaneous  condition  is,  whether  or  not  it  is  syphilis,  it  is  most  desir- 
able for  purposes  of  description  to  classify  the  lesion.    The  term 


SYPHILODERMATA  49 

syphilide  has  most  frequently  been  employed  to  designate  the 
cutaneous  manifestations  of  this  disease,  but  it  would  seem  that 
upon  etymological  grounds  the  term  syphiloderm  is  more  correct. 

Scarcely  any  two  authors  agree  upon  a  method  of  classification 
of  the  syphilodermata.  Torella,  in  1498,  described  moist  and  dry 
syphilis  with  three  forms  each,  and  since  his  time  the  nomenclature 
of  these  lesions  has  been  the  subject  of  a  vast  amount  of  discussion. 

Practically  all  modern  syphilographers  describe  the  syphilo- 
dermata occurring  in  the  various  classical  forms  of  skin  eruption, 
macules,  papules,  vesicles,  pustules,  tubercles,  etc.,  while  each  one 
divides  the  forms  into  sub-classes  according  to  his  own  observation. 

The  following  classification,  while  perhaps  open  to  some  objec- 
tions, seems  to  the  author  to  include  all  the  known  varieties  of 
the  skin  manifestations  of  syphilis. 

SYPHILODERMATA. 

I.  Macular. 

(a)  Roseolar 
(6)  Annular.    • 
(c)  Pigmentary. 
II.  Papular. 

(a)  Miliary 

(b)  Lenticular  or  flat. 

III.  Vesicular  (rare). 

IV.  Bullous  (rare). 
V.  Pustular. 

(a)  Acuminate  (large  and  small). 
(6)  Flat  (large  and  small). 
VI.  Nodular  or  Tubercular. 
VII.  Gummatous. 
While  the  above  classification  covers  the  general  characteristics 
of  syphilodermata,  it  is  not  unusual  to  find  two  or  more  varieties 
in  the  same  individual.    Thus  a  maculopapular  syphiloderm  or  a 
papulopustular  syphiloderm  frequently  is  observed. 

The  gross  appearances  of  the  cutaneous  lesions  of  syphilis  which, 
as  will  be  seen,  are  many  and  varied  and  which  occur  at  varying 
periods  following  infection  are  important  symptoms  of  the  disease 
and  will  be  discussed  in  the  chapter  on  Clinical  History. 

Histopathology. — ^The  histopathological  picture  presented  by  the 
syphilodermata,  while  showing  many  interesting  features,  is  not 
nearly  as  striking  as  the  gross  manifestations.  It  may  be  said 
of  these  lesions  that  they  truly  represent  the  reaction  of  the  tissue 
to  the  invasion  of  the  treponemata  and  show  various  combinations 
of  exudation  and  repair. 
4 


50  PATHOLOGY 

Macular  Syphiloderm. — This  type  of  lesion  microscopically  shows 
a  mild  reaction.  The  epidermis  is  either  unchanged  or  flattened 
out,  showing  obliteration  of  the  natural  ridges.  The  papillary 
layer  of  the  corium  is  the  seat  of  the  most  marked  change.  Here  the 
bloodvessels  are  found  more  or  less  dilated,  filled  with  blood  and 
surrounded  by  a  moderate  infiltration  of  lymphocytes  and  plasma 
cells.  The  endothelium  of  the  vessels  presents  a  swollen  condition 
and  in  the  adventitia  of  the  larger  ones  are  seen  round  and  spindle 
cells.  Sometimes  the  process  extends  a  little  more  deeply  and 
cellular  infiltration  is  seen  around  the  glandular  elements.  The 
treponemata  are  found  both  in  the  blood  and  the  dilated  vessels 
and  distributed  among  the  surrounding  cells. 

In  the  pigmentary  macular  syphiloderm  there  is  also  an  infiltra- 
tion into  the  adventitia  of  the  bloodvessels,  most  of  which,  according 
to  Maieff^  become  obliterated.  As  a  result  the  red  blood  corpuscles 
lose  their  pigment  which  infiltrates  the  adventitia  of  the  vessels, 
the  connective-tissue  cells  and  is  found  even  in  the  lymphatics. 
Later  the  pigmentation  is  absorbed,  leaving  the  skin  a  whitish  color. 

Papular  Syphiloderm, — The  miliaiy  papular  syphiloderm  usually 
is  associated  with  a  hair  follicle.  Histologically  the  epidermis 
is  seen  to  be  more  or  less  edematous  and  thinned,  while  there  is 
noted  an  infiltration  of  lymphocytes  with  an  occasional  plasma 
cell  and  fibroblast  around  the  hair  papilla  and  around  and  below 
the  follicle.  The  hair  sac  is  dilated  and  ruptured  by  the  pressure 
of  the  cell  infiltration.  The  bloodvessels  of  the  papilla  are  seen 
to  be  dilated,  and  are  surrounded,  as  well  as  filled,  with  cells. 
At  the  periphery  of  the  process  some  of  the  vessels  are  filled  with 
blood,  others  are  obliterated  by  thrombosis  and  appear  like  giant 
cells.  Fordyce- .  states  that  the  giant  cells  which  are  very  constant 
in  the  papular  syphilodermata  are  probably  vascular  in  origin 
rather  than  due  to  the  fusion  of  plasma  cells.  The  sebaceous  and 
sweat  glands  usually  are  involved,  while  the  latter  are  frequently 
the  seat  of  fatty  degeneration  and  are  surrounded  by  lymphocytes 
and  plasma  cells.  The  erectores  pilorum  are  also  usually  infiltrated 
with  cells.  Treponemata  are  found  about  the  basal  cells  of  the  hair 
follicle,  also  in  the  spaces  between  the  prickle  cells  of  the  rete. 

In  the  lenticular  papular  syphiloderm  the  histological  picture  is 
quite  similar  to  that  found  in  the  miliary  papular  lesion  except 
that  it  is  more  marked.  The  epidermis  shows  parakeratosis, 
edema  and  acanthosis,  while  there  usually  is  an  infiltration  of 
polymorphonuclear  leukocytes. 

While  in  the  early  stages  of  development  there  is  some  infiltration 
of  lymphocytes,  the  papule  is  mainly  due  to  epithelial  hyperplasia, 

1  Corap.  rend,  du  cong.  internat.  de  Derm,  et  de  Syphil.,  Paris,  1890,  p.  667. 

2  Recent  Studies  of  Syphilis,  St.  Louis,  1911,  p.  49. 


SYPHILODERMATA  51 

Later  the  infiltration  is  marked  in  the  rete,  in  all  layers  of  the 
corium  and  to  some  extent  in  the  subcutaneous  tissues.  In  some 
places  the  cell  infiltration  is  dense  and  in  others  disseminated  but 
is  most  marked  about  the  bloodvessels,  both  of  the  deep  and  super- 
ficial plexuses.  Most  of  the  vessels  show  thickened  walls  with 
diminution  of  the  caliber,  and  more  are  obliterated.  Giant  cells 
are  found,  but  not  as  frequently  as  in  the  miliary  papular  syphilo- 
derm.  The  sweat  glands  usually  are  surrounded  by  cell  infiltration 
as  well  as  showing  proliferation  of  the  lining  cells. 

In  the  annular  papular  syphilodermata  the  histological  picture 
varies  with  the  lesion  from  which  it  develops.  According  to  Hazen\ 
if  the  lesion  develops  from  the  follicular  syphiloderm,  the  histology 
is  in  no  way  different  from  the  parent  lesion.  If  it  develops  from 
the  lenticular  papular  lesion,  the  infiltration  around  the  bloodvessels 
is  not  so  marked,  as  seen  in  the  ordinary  papules.  However,  the 
cells  are  chiefly  plasma  cells,  especially  in  the  older  parts.  In  the 
circular  rim  both  the  corium  and  the  rete  are  markedly  thickened 
and  the  intrapapillary  processes  are  elongated  and  marked  decrease 
in  the  pigment  of  the  basal  layer  is  noted.  The  bloodvessels  and 
lymphatics  of  the  corium  and  papillse  are  found  dilated  and  marked 
infiltration,  especially  in  the  papillae  of  lymphoid  and  fixed  tissue 
cells,  with  a  few  polymorphonuclear  leukocytes  and  plasma  cells, 
is  observed.  The  rete,  especially  the  basal  layer,  is  infiltrated  with 
the  above-mentioned  cells.  In  the  central  portion  of  the  lesion 
there  is  considerable  absence  of  pigment  and  some  plasma-cell 
infiltration  about  the  bloodvessels.  According  to  Dennie,^  the 
treponemata  are  found  in  the  annular  papular  syphilodermata 
only  among  the  leukocytes  which  fill  the  spaces  between  the  prickle 
cells. 

When  marked  desquamation  of  the  epidermis  takes  place  in  the 
lenticular  papular  syphiloderm  the  lesion  is  termed  squamous 
papular  syphiloderm.  Microscopically  the  corium  is  seen  thick- 
ened and  exfoliating,  while  the  rete  is  thickened  and  proliferating. 

In  the  moist  papular  lesion  the  picture  is  very  similar  to  that 
observed  in  the  ordinary  papular  lesion,  except  that  the  process 
may  extend  deeper.  The  rete  is  usually  more  thickened  and  more 
or  less  hypertrophy  and  elongation  of  the  papillse  are  seen. 

The  histopathology  of  the  vegetating  syphiloderm  has  been 
described  by  Dennie^  as  follows:  When  divided  the  lesion  is  seen 
to  consist  of  two  parts,  an  upper,  dense,  finely  striated  portion, 
about  4  mm.  thick,  and  a  lower,  narrowed  core.  Microscopically, 
the  former  shows  many  slender  epithelial  fingers,  connected  above 
by  thin  bridges  and  below  penetrating  the  corium.     The  fingers 

1  Jour.  Cut.  Dis.,  1913,  xxxi,  p.  148. 

2  Ibid.,  1915,  xxxiii,  p.  509.  .  ^  ibij. 


52  PATHOLOGY 

consist  of  marked  hyperplasia  of  epithelial  cells,  principally  prickle 
cells. 

The  spaces  between  the  prickle  cells  in  some  areas  are  widened 
and  filled  with  leukocytes.  The  cells  of  the  neighboring  germinal 
layer  are  pushed  apart  and  communicate  with  the  underlying 
tissue,  thus  giving  a  direct  path  up  to  the  prickle  cells.  In  certain 
areas  round  spaces  are  observed  filled  with  leukocytes.  The 
papillae  of  the  corium  which  dovetail  with  the  epithelial  projections 
are  divided  histologically  into  two  parts.  The  first,  consisting  of  the 
upper  two-thirds,  is  characterized  by  numerous  parallel  capillaries 
mostly  filled  with  red  blood  cells  but  occasionally  one  filled  with 
leukocytes.  The  infiltration  here  is  mainly  lymphocytes  and  plasma 
cells,  except  in  the  top  of  the  papillae  where  some  leukocytes  are 
noted.  Many  lymph  spaces  are  seen  which  are  differentiated  from 
the  bloodvessels  by  the  thinner  walls  and  absence  of  erythrocytes. 
A  rather  frail  connective  tissue  is  seen  between  the  vessels. 

In  the  lower  part  of  the  papillae  is  seen  a  dense  infiltration  of 
plasma  cells.  Below  this  area  the  capillaries  are  seen  to  be  increased 
but  the  larger  vessels  are  not,  while  the  walls  do  not  show  much 
change,  although  they  present  a  collar  of  small  lymphocytes. 
The  coil  glands  show  a  slight  periglandular  lymphatic  infiltration. 
The  treponemata  are  not  found  in  the  dense  infiltration  nor  in  any 
place  in  the  corium  except  in  the  tips  of  the  intrapapillary  masses. 
Here  they  are  very  numerous  and  many  are  observed  half  in  the 
intrapapillary  mass  and  half  between  the  epithelial  cells.  The 
organisms  are  more  numerous  higher  up  in  the  spaces  and  with  the 
leukocytes  they  form  a  network  around  the  epithelial  cells  and 
hundreds  are  seen  in  one  field.  Between  the  prickle  cells  they  are 
not  very  numerous  but  occur  in  colonies  near  the  papillary  cones. 
They  are  found  only  occasionally  in  other  epithelial  areas.  Dennie 
states  that  the  treponemata  probably  gain  access  from  the  top  of 
the  papillary  cones  through  the  interrupted  basal  layer  of  the 
priclde  cells,  and  multiply  there.  Leukocytes  apparently  do  not 
exhibit  their  growth,  although  the  lymphocytes  and  plasma  cells 
do,  as  the  organisms  are  not  found  where  marked  infiltration  of 
these  cells  exists..  This  location  of  the  treponemata  probably 
accounts  for  the  marked  infectivity  of  this  type  of  lesion  as  the 
organisms  can  by  their  motility  migrate  to  the  outside  through  the 
intracellular  spaces. 

Vesicular  Syphiloderm. — Dennie^  has  described  the  histo- 
pathology  of  this  lesion,  stating  that  it  is  built  about  a  hair  follicle, 
and  consists  of  a  triangular  mass  of  densely  infiltrated  lymphocytes 
and  plasma  cells,  the  apex  beginning  at  the  hair  shaft,  slightly 
below  its  origin  from  the  skin,  and  its  base  below  the  fat  glands. 

1  Jour.  Cut.  Dis.,  1915,  xxxiii,  p.  509. 


SYPHILODERMATA  53 

The  corium  is  seen  to  be  pushed  out  in  all  directions,  leaving  the 
lesion  sharply  defined.  In  the  infiltrated  area  are  found  numerous 
spaces,  probably  lymphatics  but  practically  no  bloodvessels. 
Connective-tissue  fibers,  probably  of  recent  origin,  are  seen  near 
the  hair  shaft.  The  cells  of  the  basal  area  of  the  hair  follicle  show  a 
narrow  "halo"  due  to  edema  surrounding  it.  The  bloodvessels 
beyond  this  and  outside  the  area  of  infiltration  show  peri-  and  end- 
arteritis with  a  "collar"  of  small  lymphocytes.  Giant  cells  are  not 
found  and  the  epidermis  shows  little  change.  Treponemata  could 
not  be  demonstrated  by  Levaditi's  method. 

Bullous  Syphiloderm. — As  far  as  the  author  is  aware  no  adequate 
description  of  the  histopathology  of  this  lesion  in  the  acquired 
form  of  syphilis  has  been  made,  but  as  it  differs  grossly  in  no  respect 
from  the  same  lesion  in  the  congenital  form,  its  microscopic  picture 
undoubtedly  is  the  same.  A  description  of  the  histopathology  of 
this  lesion  as  observed  in  congenital  syphilis  will  be  found  in  the 
portion  of  the  book  dealing  with  that  subject. 

Pustular  Syphiloderm. — The  microscopic  picture  of  this  lesion 
varies  with  the  extent  of  the  process  and  is  essentially  the  same 
as  a  papular  syphiloderm  to  which  is  added  the  change  due  to 
pyogenic  organisms. 

The  pustular  syphiloderm  may  or  may  not  be  connected  with  a 
hair  follicle.  It  is,  however,  well  defined,  is  sometimes  limited 
to  the  corium  and  sometimes  invades  the  connective  tissue.  The 
condition  does  not  vary  materially  from  other  non-syphilitic  pus- 
tular lesions  such  as  variola.  The  pus  cells  are  found  between  the 
strata  of  the  epidermis,  the  rete  or  the  corium  forming  the  base, 
or  sometimes  the  suppuration  extends  through  the  latter. 

In  the  rupial  syphiloderm  a  marked  parakeratosis  with  infil- 
tration of  leukocytes  of  the  entire  corium  is  observed.  The  crust 
is  formed  of  aggregations  of  cells,  coagulated  serum,  and  detritis. 

Nodular  Syphiloderm. — ^The  histopathology  of  this  type  of 
syphilitic  lesion  diifers  but  little,  except  in  degree,  from  that  of  the 
papular  syphiloderm.  With  the  low  powers  of  the  microscope 
alternate  light  and  dark  areas  are  seen  involving  the  entire  cutis 
from  the  epidermis  to  the  connective  tissue.  The  high  powers 
reveal  the  fact  that  the  dark  areas  are  composed  of  cellular  infiltra- 
tion, while  the  light  areas  are  made  up  of  bloodvessels.  The  latter 
are  increased  in  number  and  many  of  them  obliterated,  their  former 
site  being  shown  by  solid  cords  and  giant  cells.  The  nodular 
syphiloderm  does  not  develop  as  rapidly  as  the  papular  lesion,  it 
persists  longer,  and  is  followed  by  atrophic  and  necrotic  changes 
which  go  on  to  ulceration. 

Gummatous  Syphiloderm. — This  variety  of  the  syphilodermata 
presents  extensive  vascular  change  and  diffuse  infiltration.  The 
walls  of  the  bloodvessels  are  thickened  by  an  endarteritis,  while 


54  PATHOLOGY 

the  caliber  is  reduced  or  obliterated.  The  infiltration  consists  of 
lymphocytes,  plasma  cells,  and  hyperplastic  fibroblasts.  Areas 
of  caseation  occasionally  are  observed,  which  contain  poorly 
staining  nuclei,  fatty  droplets,  pigmentary  granules,  disintegrated 
elastic  fibers  and  colloidal  granulations.  Giant  cells  rarely  are 
observed  in  this  type  of  lesion. 

MUCOUS  MEMBRANES. 

The  mucous  membranes  of  the  various  openings  of  the  body, 
mouth,  nostrils,  vagina  and  anus,  are  affected  with  syphilitic 
manifestations  very  similar  to  those  occurring  on  the  skin,  although 
not  all  varieties  are  observed  on  the  mucous  membranes.  These 
lesions  differ  from  the  syphilodermata  only  as  the  physical  and 
anatomical  conditions  differ. 

Such  lesions  are  usually  termed  syphilides  of  the  mucous  mem- 
brane or  mucous  syyliiUdes,  but  as  the  term  syphilide  is  used  by 
many  writers  to  designate  the  skin  manifestations  of  syphilis,  as 
well  as  those  of  the  mucous  membranes,  it  seems  most  desirable  to 
have  a  name  which  applies  alone  to  the  lesions  of  the  latter.  The 
term  syyhilomycoderm  {sypkilis,  syphilis;  mycoderm,  mucous  mem- 
brane, fjivKTis,  mucous;  bkpjxa,  skin)  is  therefore  proposed. 

As  with  the  syphilodermata,  so  with  the  lesions  of  the  mucous 
membranes,  scarcely  any  two  syphilographers  agree  concerning 
their  classification.  The  following  seems  to  the  author  to  cover  the 
principal  varieties  of  these  lesions: 

I.  Macular. 

(a)  Erythematous. 
(6)  Erosive. 

II.  Papular. 

(a)  Erosive. 

(6)  Ulcerative. 

(c)  Vegetative. 

{d)  Squamous. 

(e)  Leukoplakia. 
III.  Gummatous. 
The  gross  appearance  of  the  lesions  of  the  mucous  membranes  as 
well   as   the   gross   appearance  of   the   syphilodermata  constitute 
important   symptoms   of  the   disease  and   therefore   will    also   be 
described  in  the  chapter  on  Clinical  History. 

The  histopathological  picture  observed  in  these  lesions  presents 
little  that  is  different  from  that  seen  in  the  homologous  syphilo- 
dermata. There  is  found  the  same  general  reaction  of  the  tissues 
to  the  invading  organism,  infiltration  of  cellular  elements,  swelling 
of  the  endothelium  of  the  bloodvessels,  proliferation  of  the  fixed 
cells  and  more  or  less  thickening  and  destruction  of  the  epithelial  cells. 


CHAPTER  V. 
CLINICAL  HISTORY. 

Syphilis  is  a  chronic  disease  caused  by  a  specific  microorganism, 
the  Treponema  palhdum,  which  in  the  acquired  form  begins  with  a 
local  lesion,  later  becomes  systemic,  and  spreads  through  the 
lymphatics  and  blood  to  the  various  tissues  and  organs  of  the  body. 
In  the  congenital  form  and  in  certain  cases  of  experimental  and 
accidental  syphilis  the  local  lesion  is  not  manifest.  Throughout  the 
entire  course  of  the  disease  syphilis  tends  to  cellular  proliferation 
and  the  formation  of  new  connective  tissue  and  at  certain  times 
to  development  of  fibrous  and  caseous  tumors. 

Jonathan  Hutchinson^  has  remarked  that  syphilis  has  long  been 
said  to  constitute  in  itself  an  epitome  of  pathology  and  adds,  "there 
is  scarcely  a  malady  which  has  received  a  name  which  may  not 
be  simulated  by  it,  and  still  fewer  which  it  may  not  modify." 

Ricord's  Stages. — As  pointed  out  in  Chapter  I,  Ricord  divided 
syphilis  into  three  stages:  primary,  secondary,  and  tertiary,  to 
which  Fournier  later  added  a  fourth  or  quartenary  stage.  The 
primary  stage,  according  to  the  great  syphilologist,  includes  the 
development  of  the  chancre  and  the  adjacent  adenopathy.  During 
the  secondary  period  the  infection  becomes  systemic  and  the  various 
superficial  lesions  of  the  skin  and  mucous  membranes  are  manifest. 
During  this  stage  also  occur  orchitis,  alopecia,  and  iritis.  The 
tertiary  stage  is  marked  by  the  involvement  of  the  inner  structures 
of  the  body  such  as  the  bones,  joints,  and  viscera.  The  quartenary 
stage  of  Fournier  consists  of  the  so-called  parasyphilitic  diseases, 
paresis  and  tabes,  which  we  now  know  to  be  true  syphilis  of  the 
brain  and  spinal  cord. 

Ricord's  Classification  Inadequate. — While  the  division  of  syphilis 
into  stages  by  Ricord  was  a  long  step  in  advance,  and  has  been 
followed  by  most  «syphilographers  up  to  the  present  time,  it  cannot 
today  be  considered  scientific.  Even  at  so  early  a  date  as  1843 
Cazenave^  objected  to  Ricord's  classification,  stating  that  any 
lesions  of  syphilis  may  occur  at  any  time  no  matter  how  near  or  how 
far  it  is  removed  from  the  first  infection.    Hyde^  also  objected  to 

1  Power  and  Murphy:  System  of  Syphilis,   London,   1908,   Introduction,  p.  xvii. 

2  Quoted  by  Baumler:  Encyclopedia  of  the  Practice  of  Medicine,  New  York, 
1875,  iii,  p.  27. 

2  Morrow:  A  System  of  Geni to-urinary  Diseases,  Syphilology  and  Dermatology, 
New  York,  1898,  ii,  p.  22. 


56  CLINICAL  HISTORY 

Ricord's  classification,  stating  that  it  had  served  its  day.  He 
proceeded  to  point  out  that  there  is  no  sharp  boundary  line  between 
the  various  manifestations  of  syphilis,  that  from  the  instant  of 
infection  to  the  terminal  phenomena  there  is  a  gradual  advance  of 
the  disease.  These  statements  in  the  light  of  modern  knowledge 
of  the  Treponema  pallidum  are  seen  to  be  most  true. 

On  purely  anatomical  grounds  it  is  readily  seen  that  we  must 
discard  the  stages  of  Ricord.  The  non-gummatous  orchitis  has 
been  classified  by  some  as  secondary  and  by  others  as  tertiary. 
So  why  attempt  to  give  it  a  chronological  classification?  Let  it 
be  termed  a  syphilitic  orchitis  or  diffuse  syphilitic  inflammation 
of  the  testicle,  and  state  that  it  may  occur  at  any  period  subsequent 
to  the  systemic  involvement.  Another  reason  for  abandoning 
Ricord's  classification  is  that  in  hereditary  syphilis  and  in  syphilis 
of  rabbits  produced  by  intracardial  inoculation  as  well  as  in  such 
cases  as  reported  by  Fordyce^  in  which  in  one  instance  infection 
accidentally  occurred  by  a  hypodermic  needle  which  had  been  used 
for  collecting  blood  for  the  Wassermann  reaction  and  in  another 
case  by  blood  transfusion,  no  so-called  primary  stage  exists.  It 
would  therefore  seem  that  the  only  scientific  classification  of  the 
phenomena  of  syphilis  is  one  based  upon  anatomic  and  symptomatic 
grounds. 

Development  and  Course. ^ — It  is  an  almost  universally  accepted 
belief  today  that  there  must  be  a  solution  of  the  continuity  of  the 
epithelium  for  the  Treponema  pallidum  to  gain  entrance  to  the 
body.  And  after  this  direful  germ  has  once  penetrated  the  epithelial 
barrier,  no  matter  in  what  location,  there  is  a  period  during  which 
it  gives  no  outward  evidence  of  its  presence,  and  its  host  goes  his 
way,  blissfully  ignorant  of  what  is  to  follow.  This  time,  known 
as  the  incubation  period,  varies  from  ten  days  to  three  months, 
although  the  average  duration  is  from  three  to  four  weeks.  Bronson^ 
states  that  Diday  once  saw  a  case  with  an  incubation  period  of 
but  twenty-four  hours,  and  that  LeFort  mentions  three  cases  with 
this  period  not  exceeding  seventy-two  hours.  In  the  light  of 
modern  knowledge  of  the  infecting  organism  these  reports  of  such 
extremely  short  incubation  periods  must  be  taken  with  great  reserve. 

There  are  a  number  of  causes  operating  which  undoubtedly 
determine  the  length  of  the  incubation  period.  The  most  important 
of  these  would  seem  to  be :  the  number  of  organisms  inoculated,  the 
condition  of  the  point  of  inoculation  as  to  vascularity,  etc.,  the 
nature  and  amount  of  the  abrasion,  the  natural  resistance  of  the 
individual  and  the  virulence  of  the  organisms.     This  virulence 

1  Am.  Jour.  Med.  Sc,  1915,  cxlix,  p.  781. 

2  Morrow:  A  System  of  Genito-urinary  Diseases,  Syphilology  and  Dermatology, 
New  York,  1898,  ii,  p.  73. 


DEVELOPMENT  AND  COURSE  57 

would  seem  to  depend  upon  the  condition  of  the  lesion  from  which 
the  organisms  are  derived,  that  is,  the  age  of  the  lesion,  whether  or 
not  it  has  been  treated,  etc.,  and  when  inoculation  takes  place 
through  intermediate  contact  upon  the  nature  and  condition  of  the 
object  which  carries  the  organisms  and  the  length  of  time  which 
elapses  between  the  contact  with  the  infected  and  the  non-infected 
individual. 

During  this  varying  incubation  period  the  treponemata  have 
been  multiplying  and  in  all  probability  spreading  by  way  of  the 
I>TQph  channels  and  bloodvessels,  although  all  evidence  of  the 
abrasion  in  the  epithelium  may  have  disappeared.  However, 
at  the  end  of  this  time  the  chancre  appears  at  the  sight  of  the 
inoculation.  This  lesion,  which  usually  begins  with  a  papule, 
takes  many  forms,  which  will  be  described  later,  lasts  for  a  varying 
period  and  gives  no  evidence  of  the  severity  of  the  condition  which 
is  to  follow.  There  is  scarcely  any  pain  connected  with  it,  no 
apparent  systemic  involvement,  very  little  discomfort,  and  the 
patient  usually  leads  his  accustomed  life.  There  is  soon,  however, 
evidence  that  the  treponemata  have  left  the  portal  of  entry  and 
have  invaded  the  lymphatic  system.  The  adjacent  glands  become 
enlarged  and  hard,  although  usually  not  painful  and  they  rarely 
suppurate. 

Following  the  appearance  of  this  adenopathy  there  is  another 
period  of  apparent  quiescence,  known  as  the  second  incubation 
period,  which  averages  in  length  from  six  to  seven  weeks,  although 
it  may  be  shorter  or  be  prolonged.  In  patients  who  are  suf- 
fering from  other  diseases,  or  who  are  debilitated  from  excesses, 
the  period  is  usually  shortened,  while  specific  treatment  will  tend  to 
make  it  longer.  It  has  been  stated  that  this  so-called  second 
incubation  period  is  usually  shorter  following  extragenital  than 
genital  chancres  but  this  contention  lacks  confirmation.  However, 
during  this  time  the  germs  have  been  multiplying  and  spreading 
through  the  lymph  and  blood,  and  presently  all  doubt  of  the  nature 
of  the  disease  is  vanished  by  the  appearance  of  the  cutaneous 
manifestations.  Although  the  vast  majority  of  chancres,  which 
receive  no  specific  treatment,  are  followed  by  syphilodermata,  this 
is  not  true  in  all  cases,  and  in  the  days  when  physicians  relied  for 
a  diagnosis  solely  upon  the  development  of  the  so-called  secondaries 
many  errors  were  made.  These  syphilodermata,  while  usually 
easily  recognized,  may  simulate  almost  any  form  of  dermatological 
lesion.  The  lining  membranes  of  the  mouth  and  throat  now  usually 
develop  lesions  of  varying  appearance,  while  accompanying  these 
conditions  may  be  fever,  headache,  and  other  symptoms  of  more  or 
less  severity. 

From  now  on  the  disease  is  most  protean.    The  acute  symptoms 


58  CLINICAL  HISTORY 

may  disappear  either  with  or  without  treatment  and  the  causative 
organisms  apparently  He  dormant  for  years  only  to  break  out  in 
unexpected  places.  As  stated  above,  there  is  no  tissue  or  organ 
of  the  body  which  is  immune  to  their  attack.  The  heart  and  blood- 
vessels very  often  are  involved,  even  early  in  the  course  of  the  disease, 
and  various  symptoms  arise  which  may  or  may  not  be  recognized 
as  syphilitic.  Nephritis  due  to  the  treponemata  is  a  frequent 
symptom,  especially  during  the  acute  outbreak.  Many  cases  of 
syphihs  of  the  lungs  have  undoubtedly  been  diagnosed  tuberculosis, 
while  the  liver  is  not  infrequently  involved,  jaundice,  acites  and 
other  symptoms  resulting.  The  bones  and  joints  are  often  the  seat 
of  the  infection  which  is  manifested  by  pain,  tenderness,  swelling 
and  other  symptoms. 

The  most  important  portion  of  the  body  to  be  invaded  by  the 
organisms  of  syphilis,  however,  is  the  nervous  system.  Any  or  all 
portions  of  the  nervous  system  may  be  attacked,  the  meninges,  the 
brain,  the  spinal  cord  or  the  nerves,  and  in  recent  years  it  has  been 
shown  that  such  invasion  may  occur  even  as  early  as  the  time  of 
the  chancre. 

Although  involvement  of  the  bones,  viscera,  nervous  system,  etc., 
may  take  place  early  and  probably  usually  does,  symptoms  refer- 
able to  such  involvement  as  a  rule  are  among  the  late  manifestations 
of  the  disease. 

Thus  the  brain  substance  may  be  attacked,  six,  eight,  ten  or 
more  years  after  the  chancre,  paresis  result  and  the  chapter  close 
with  death. 

CHANCRE. 

Development. — The  term  chancre  is  a  French  word  derived  from 
the  Latin  cancer.  This  lesion,  which  in  the  acquired  form  of  syphilis 
is  the  first  manifestation  of  the  disease,  usually  begins  as  a  small 
reddish  spot  at  the  site  of  inoculation  and  soon  develops  into  a 
papule.  It  may  or  may  not  at  this  time  convey  to  the  palpating 
fingers  a  sense  of  resistance.  The  surface  may  be  moist  with  a 
light,  sticky,  clear,  sanious,  fluid  or  it  may  be  perfectly  dry.  The 
attention  of  the  individual  may  first  have  been  called  to  it  by 
itching,  or  it  may  have  been  observed  by  him  as  what  is  vulgarly 
known  as  a  "hair  cut."  The  lesion  is  generally  nearly  circular  in 
outline  and  of  a  dark  red  color,  which  later  changes  to  gray.  It 
varies  greatly  in  size,  sometimes  being  so  small  as  to  pass  unnoticed, 
and  again  it  may  be  4  or  5  cm.  or  over  in  diameter.  While  this 
lesion  of  syphilis  is  usually  single,  it  may  be  multiple.  It  would  seem 
that  the  number  usually  depends  upon  the  number  of  abrasions 
which  exist  at  the  time  of  inoculation,  but  multiple  chancres  may 
occur  by  auto-inoculation. 


CHANCRE  59 

In  a  few  days  a  hard  mass  or  induration  develops  in  the  vast 
majority  of  cases  at  the  base  of  the  chancre.  This  varies  greatly 
in  size  and  shape.  It  may  be  so  slight  as  to  be  undetected  except 
by  the  most  skilful  palpation,  or  it  may  be  hard  and  nodular,  being 
readily  recognized  on  sight.  At  times  it  is  thin  and  lamellar, 
resembling  a  piece  of  parchment  or  it  may  be  of  annular  shape, 
forming  a  ring  around  the  sore.  The  induration  is  not  inflammation, 
as  it  takes  place  without  the  cardinal  symptoms  of  that  pathological 
process.  It  varies  greatly  with  the  location  of  the  chancre.  If  the 
latter  is  in  a  spot  where  the  tissues  are  firm  and  resistant,  it  is  much 
more  difficult  of  detection.  Generally  speaking,  when  the  chancre 
is  located  on  mucous  membrane  the  induration  may  be  felt  more 
easily  than  when  the  skin  is  the  seat  of  the  infection.  The  induration 
usually  lasts  after  the  sore  is  healed.  The  sore  itself  generally  heals 
even  without  treatment  and  leaves  little  or  no  trace  of  its  existence. 
This  is  probably  due  to  a  local  acquired  immunity  which  causes  the 
Treponema  pallidum  to  die  out  in  the  sore.  However,  a  pigmented 
spot  may  persist  for  some  time  and  occasionally  there  may  be  a 
white  spot  left,  due  to  loss  of  tissue,  which  may  last  for  years. 

Location. — Genital. — The  most  frequent  location  of  the  chancre 
in  men  is  the  balano-preputial  fold.  This  is  undoubtedly  due  to  the 
fact  that  in  this  location  slight  abrasions  most  frequently  occur. 
The  location,  which  next  to  the  above,  is  most  often  affected  is  the 
lining  mucous  membrane  of  the  prejmce.  A  chancre  of  this  location 
often  cannot  be  observed,  owing  to  the  presence  of  a  phimosis, 
which  may  or  may  not  be  due  to  the  lesion  itself.  In  such  a  case 
circumcision  should  be  performed  to  permit  of  an  accurate  diagnosis. 
The  preputial  orifice  is  next  most  frequently  attacked-  by  the 
syphilitic  organism,  while  the  order  of  frequency  of  other  genital 
chancres  in  the  male  is  as  follows:  frenum,  skin  of  penis,  glans  penis, 
urinary  meatus,  scrotum,  prescrotal  angle,  and  urethra. 

When  the  preputial  orifice  is  the  seat  of  the  infection,  the  sore 
gives  to  the  prepuce  the  appearance  of  having  been  split.  At  first 
the  splits  look  like  mere  scratches  which  later  become  indurated 
and  the  prepuce  thickened. 

A  chancre  of  the  skin  of  the  penis  begins  as  a  small  abrasion 
which  gradually  spreads  until  it  may  attain  a  diameter  of  2  or  3  cm. 
The  edges  are  hard  and  the  induration  is  thin,  parchment-like  and 
quite  easily  detected  by  palpation. 

When  the  surface  of  the  glans  penis  is  the  seat  of  a  chancre  it 
begins  as  a  flat  erythematous  spot,  which  in  a  short  time  becomes 
depressed  in  the  centre  with  hard,  indurated  edges. 

Either  one  or  both  lips  of  the  urinary  meatus  may  be  inoculated 
with  the  Treponema  pallidum  and  a  chancre  result.  However, 
that  both  are  aft'ected  is  the  rule.    Induration  is  invariably  present, 


60  CLINICAL  HLSTORY 

though  slight.  A  scanty,  viscid,  discharge  is  found  which  generally 
glues  the  lips  together.  There  is  usually  some  impediment  to  the 
flow  of  urine,  which,  however,  disappears  when  the  lesion  heals. 

Chancre  of  the  scrotum  usually  begins  with  a  small,  circular, 
reddish  spot  which  gradually  spreads  in  size.  There  is  soon  des- 
quamation of  the  superficial  epithelium  and  small  cracks  occur 
which  coalesce,  forming  a  circular  ulcer.  This  ulcer  is  usually  not 
deep  but  has  considerable  induration.  Chancres  of  the  prescrotal 
angle  are  similar. 

Ricord^  taught  that  the  urethra  frequently  lodged  the  syphilitic 
chancre  and  that  it  was  due  to  this  fact  that  many  cases  of  syphilis 
remained  unrecognized  until  further  symptoms  of  the  disease 
appeared.  The  majority  of  urethral  chancres  are  just  within  the 
meatus  or  in  the  fossa  navicularis,  but  may  be  so  far  from  the 
opening  that  they  cannot  be  seen  except  by  the  aid  of  the  endo- 
scope. 

Genital  chancres  in  the  female  are  found  most  frequently  on  the 
labia  majora  and  vary  according  to  their  location,  whether  on  the 
internal  or  external  aspect,  or  on  the  free  margin.  In  these  locations 
the  chancre  quite  frequently  is  accompanied  by  an  edema  of  the 
part.  This  is  due  to  a  superficial  lymphangitis  and  may  result  in 
hyperplasia.  If  both  labia  are  affected,  it  is  usually  due  to  a  double 
infection  and  not  to  spreading  from  one  labium  to  the  other. 
According  to  Fournier,  other  genital  chancres  in  the  female  occur 
in  the  order  of  their  frequency  on  the  labia  minora,  fourchette, 
cervix,  region  of  clitoris,  vestibule  of  the  vagina,  meatus  urinarius, 
upper  commissure  of  the  vulva  and  vagina. 

Chancre  of  the  cervix  is  perhaps  relatively  frequent,  but  is  quite 
often  unrecognized.  That  a  chancre  in  this  location  is  more  common 
than  chancre  of  some  other  regions  is  doubtless  due  to  the  frequency 
of  abrasions  of  the  mucous  membrane  of  the  cervix,  and  obviously 
it  may  easily  be  overlooked,  owing  to  the  anatomical  construction 
of  the  parts.  It  is  typical  of  chancre  of  the  cervix  that  the  edges 
are  thick  and  sloping.  It  is  usually  round  and  smooth,  with  a 
glistening,  dry  floor,  and  bleeds  easily  when  touched.  A  striking 
characteristic  of  chancre  of  the  cervix  is  the  rapidity  of  its  healing 
which  may  occur  before  any  other  manifestations  of  syphilis 
appear. 

That  vaginal  chancres  are  extremely  rare  is  not  to  be  wondered  at, 
owing  (1)  to  the  comparative  toughness  of  the  mucous  membrane 
of  this  region,  which  makes  abrasions  infrequent,  and  (2)  to  the 
normal  secretions  which  bathe  the  vagina  and  probably  act  as  a 
treponemacide. 

1  Letters  on  Syphilis,  American  edition,  Philadelphia,  1857,  p.  101. 


CHANCRE 


61 


Perigenital. — To  this  class  of  syphilitic  chancres  belong  those 
of  the  anus  and  rectum,  the  groin,  the  upper  and  inner  aspect  of  the 
thigh,  and  symphysis  pubis. 

Chancres  of  the  anus  and  rectum  may  occur,  and  usually  do,  in 
men  as  the  result  of  sodomy.  In  women  intercourse  per  rectum 
may  be  the  cause,  or  a  chancre  of  the  anus  may  follow  the  flowing  of 
vaginal  secretions  and  semen,  carrying  the  Treponema  pallidum 
over  the  part.  Chancres  of  these  locations  may  result  from  inter- 
mediate contact  with  infected  enema  syringes,  specula,  etc.  A 
chancre  situated  at  the  margin  of  the  anus  appears  as  a  thickened, 
ulcerated  fissure.  It  is  of  a  rose-red  tint  and  shows  but  slight 
induration.  When  located  within  the  rectum  a  chancre  shows  a 
deep  eroding  or  ulcerating  surface  which  is  more  or  less  smooth. 
Induration,  if  present,  is  difficult  of  detection. 


Fig.  2. — Chancre  of  the  nose. 


Venereal  chancres  of  the  groin  and  upper  and  inner  aspect  of  the 
thigh  in  women  may  occur  from  an  attempt  at  coitus  or  in  both  men 
and  women  from  unnatural  practices.  Such  chancres  start  as  small 
papules  which  gradually  increase  in  size  to  three  or  more  centimeters 
in  diameter.  They  are  usually  flat  and  dry,  although  they  may  be 
eroded  and  moist.  Induration  may  be  present,  though  difficult  of 
detection. 

Extragenital. — There  is  scarcely  any  portion  of  the  body  which 
may  not  be  the  seat  of  syphilitic  chancre.  However,  the  most 
common  locations  of  extragenital  chancres  in  the  order  of  their 
frequency  are,  the  lips,  tonsils,  tongue,  breasts,  eyelids,  and  fingers. 
Such  locations  as  the  nose  and  great  toe,  as  cited  in  Chapter  III,  are 
merely  medical  curiosities,  but  show  that  a  suspicious-looking  sore 


62 


CLINICAL  HISTORY 


of  any  part  of  the  body  should  be  made  the  object  of  most  careful 
examinations. 


^1 

% 

^^^^^^^^^^^^^^^^Hm^^i 

^'" 

^^^IK 

■i 

Fig.  3. — Chancre  of  the  Hp. 


A  labial  chancre  generally  appears  as  a  fissure  or  cleft  but  may 
appear  as  a  papule.  There  is  usually  considerable  induration  and 
there  may  be  ulceration.  It  may  be  so  small  as  to  pass  unnoticed, 
or  thought  of  as  a  crack  due  to  cold,  or  it  may  be  so  large  as  to 
disfigure  the  face. 


Fig.  4. — Chancre  of  the  Hp. 


While  chancre  of  the  tonsil  is  of  comparatively  frequent  occurrence, 
its  importance  lies  more  in  the  great  danger  of  it  being  incorrectly 
diagnosed.    In  this  region  the  lesion  partakes  of  the  usual  induration 


CHANCRE 


63 


of  other  chancres.     It  is  usually  unilateral  but  may  be  bilateral. 
The  surface  is  generally  eroded  and  may  ulcerate.     A  grayish 


Fig.  5. — Chancre  of  the  tongue. 


Fig.  6. — Chancre  of  the  eyeUd. 


64  CLINICAL  HISTORY 

membrane  may  be  present,  which  has  often  caused  the  diagnosis  of 
diphtheria  to  be  made.  Certain  cases  may  become  phagedenic  or 
gangrenous,  when  there  may  be  considerable  loss  of  tissue.  More 
or  less  pain  and  difficulty  in  swallowing  are  experienced. 

A  lingual  chancre  is  ordinarily  seen  as  an  oval,  flat  surface  or 
as  a  nodule  with  thickened  edges  and  marked  induration.  It  is 
usually  eroded,  and  if  on  the  tip,  presents  the  appearance  of  the 
tongue  having  been  cut  off. 

Chancre  of  the  breast  may  be  situated  on  the  nipple,  on  the 
areola,  or  on  the  breast  itself  and  presents  no  peculiarities  not  found 
in  chancres  of  other  localities,  except  perhaps  a  greater  tendency  to 
multiplicity.    Chancre  of  the  breast  has  been  observed  in  men. 

When  the  chancre  develops  on  the  eyelid  there  is  usually  more 
or  less  deformity,  depending  upon  the  extent  of  the  lesion.  Either 
one  or  both  lids  may  be  affected,  the  chancre  starting  on  the  skin 


Fig.  7. — Chancre  of  the  finger. 

or  palpebral  conjunctiva,  and  rarely  spreading  to  the  ocular  con- 
junctiva. In  the  beginning  the  chancre  usually  appears  as  a  papule 
which  soon  ulcerates  and  becomes  indurated  to  a  marked  degree. 

Chancre  of  the  finger  presents  a  class  of  syphilitic  lesion,  which, 
although  probably  m.ore  frequent  in  physicians  than  any  other 
class  of  individuals,  very  often  remains  undiagnosed  until  other 
manifestations  of  the  disease  occur.  The  usual  location  of  chancre 
of  the  finger  is  on  the  site  of  a  hang-nail,  but  it  may  be  at  any  place 
where  the  treponema  may  gain  entrance  through  a  scratch  or  other 
abrasion.  The  most  striking  feature  of  digital  chancre  is  the  absence 
of  demonstrable  induration.  This  is  probably  due  to  the  density 
of  the  tissues.  However,  there  usually  is  swelling  of  the  entire 
finger.  Quite  frequently  the  chancre  may  surround  the  nail  in 
a  horseshoe  shape,  destroying  the  nail  and  leaving  considerable 
malformation  of  the  finger-tip.*^ 


CHANCRE  65 

Varieties. ^ — It  will  be  seen  from  the  above  that  the  syphilitic 
chancre  does  not  exist  as  a  typical  pathological  lesion,  that  it  may 
assume  many  shapes  and  forms.  There  are,  however,  a  number  of 
fairly  constant  varieties  which,  to  a  large  extent,  depend  upon 
their  location. 

The  first  is  the  indurated  papule.  This  lesion  begins  as  a  slight, 
dark  red  elevation  which  may  attain  the  size  of  2  cm.  or  more  in 
diameter.  It  is  dry  and  hard  and  the  surface  is  not  broken  through- 
out the  entire  course  of  the  lesion. 

The  eroded  chancre  is  probably  the  most  frequent  form  of  this 
sore.  It  has  the  appearance  of  a  rounded  or  oval  spot  with  a  smooth, 
raw  surface.  The  edges  are  not  elevated  above  the  surrounding 
tissue,  and  while  the  centre  is  usually  concave,  it  may  be  convex 
or  dome-shaped.  Such  a  chancre  may  be  as  small  as  a  split  pea  or 
as  large  as  a  five-cent  piece  in  diameter. 

Quite  frequently  a  chancre  assumes  the  form  of  an  ulcerating 
sore  which  may  involve  only  the  superficial  layers  or  may  burrow 
deep  into  the  tissues.  Such  a  lesion  has  been  termed  a  Hunterian 
chancre.  Induration  is  usually  quite  marked  in  the  beginning  but 
may  be  covered  with  a  grayish  false  membrane,  and  a  slight,  thin, 
sanious  exudate  is  present. 

Occasionally  in  the  beginning  a  chancre  has  the  appearance  of 
the  mark  left  after  the  application  of  a  stick  of  silver  nitrate. 
This  type  of  lesion  has  been  called  the  silvery  spot.  It  gradually 
assumes  a  dark  yellow  color  and  considerable  induration  exists. 

A  recurring  or  relapsing  chancre  (chancre  redux)  is  a  lesion, 
probably  a  gumma,  which  has  all  the  appearance  of  an  original 
chancre  and  which  develops  on  or  near  the  site  of  a  previous  chancre. 
It  may  occur  at  any  time,  from  a  few  weeks  to  ten  or  twelve  years 
or  longer  after  the  healing  of  the  first  sore.  The  surface  usually 
remains  intact  but  it  may  become  eroded. 

Complications  of  Chancres. — A  chancre  may  be  modified  in  appear- 
ance and  course  by  inflammation,  complication  with  chancroid  or 
by  phagedena. 

Inflammation  of  the  chancre  may  be  due  to  the  application  of 
caustics  or  to  the  presence  of  pyogenic  organisms.  In  either  case 
the  appearance  of  the  lesion  will  be  modified  greatly.  The  sore  and 
adjacent  tissues  become  red  and  swollen,  while  pain,  which  is  rare 
in  uncomplicated  chancre,  may  be  most  intense. 

The  complication  of  a  chancre  with  chancroid,  which  is  known  as 
a  mixed  sore,  is  not  infrequent.  The  double  infection  may  occur 
at  the  same  time  from  the  same  source  or  the  chancre  may  be 
subsequently  inoculated  with  the  bacillus  of  Ducrey,  the  causative 
agent  of  chancroid.  In  the  former  case  the  typical  chancroidal 
ulcer,  which  develops  first,  owing  to  the  shorter  incubation  period, 
5 


66 


CLINICAL  HISTORY 


is  gradually  surrounded  with  the  induration  of  the  syphilitic  lesion. 
While  if  the  chancre  is  later  infected  with  the  chancroid  bacillus, 
the  induration  is  destroyed  by  ulceration. 

The  most  serious  complication  of  chancre  is  phagedena,  which, 
fortunately,  is  rather  rare.  This  condition  may  develop  in  a  chancre 
at  the  very  beginning  or  it  may  not  appear  until  quite  late.  It  is 
probably  caused  by  a  mixed  infection  of  pyogenic  bacteria,  although 
any  lowering  of  the  vitality,  such  as  that  resulting  from  drunkenness, 
diabetes,  nephritis,  etc.,  may  predispose  the  individual  to  it.  The 
ulcerative  process  usually  spreads  on  all  sides  and  deep  into  the 
tissues,  although  it  may  progress  in  only  one  direction  (serpiginous 
ulceration).     The  sore  is  irregular  with  markedly  congested  and 


Fig.  8. — Phagedena. 


edematous  edges.  It  bleeds  easily  and  may  even  erode  through 
a  vessel  of  some  size,  causing  considerable  hemorrhage.  There  may 
be  sloughing  and  loss  of  tissue. 


LYMPHATIC  GLANDS. 

As  stated  above,  the  enlargement  of  the  lymphatic  glands  adjacent 
to  the  chancre  is  an  almost  universal  occurrence.  Ricord  said, 
"  Pas  de  chancre  infectant  sans  huhon."  While  the  lymphatic  glands 
nearest  the  initial  lesion  are  the  ones  usually  affected,  this  is  not 
necessarily  the  case,  as  the  glands  involved  are  those  which  receive 
the  afferent  vessels  which  originate  at  the  site  of  the  chancre.    The 


LYMPHATIC  GLANDS  67 

following  table  shows  the  glands  which,  as  a  rule,  are  enlarged  with 
chancres  of  various  localities: 

Site  of  Chancre.  Glands  Involved. 

Genitals,  buttocks,  aiw»s,  thigh,  leg,  foot.     Inguinal. 

Tongue.  Submaxillary  or  submental. 

Lip.  Submaxillary. 

Chin.  Submental. 

Tonsil.  Deep  cervical. 

Finger,  hand,  forearm.  '  Epitrochlear  and  axillary. 

Arm,  breast.  Axillary. 

No  glandular  enlargement  which  is  palpable  is  produced  by 
chancre  of  the  cervix,  but  without  doubt  the  internal  iliac  glands 
are  enlarged  with  chancre  of  this  location. 

The  lymphatic  enlargement  usually  is  observed  early  in  the 
course  of  the  disease,  during  the  first  week  following  the  appearance 
of  the  chancre,  as  a  rule,  but  may  be  seen  as  late  as  the  second  week. 
While  sometimes  only  one  gland  may  be  felt,  it  is  usual  for  several 
to  be  involved.  They  appear  as  hard,  round,  freely  movable  nodules, 
which  are  sharply  defined.  They  may  pass  unnoticed  by  the  patient, 
as  there  rarely  is  any  pain. 

When  the  chancre  develops  on  those  locations  draining  into  the 
inguinal  glands  the  so-called  syphilitic  bubo  is  formed.  The  enlarge- 
ment may  be  unilateral  but  usually  is  observed  in  both  groins. 
Although  the  superficial  inguinal  glands  are  generally  the  only  ones 
which  can  be  felt,  it  has  been  determined  in  persons  suffering  with 
genital  chancres,  who  have  met  violent  deaths,  that  other  glands  also 
are  involved.  This  undoubtedly  is  the  case  in  chancres  of  other 
localities  as  well.  As  a  rule  no  suppuration  occurs,  but  in  "mixed 
sores"  and  in  ulcerating  chancres  this  condition  may  be  found. 

Aside  from  the  lymphatic  enlargement  just  described,  and 
obviously  depending  upon  the  chancre  of  the  region  drained  by 
the  afferent  vessels  of  the  glands  involved,  the  Treponema  pallidupa 
seems  to  have  a  predilection  for  lymphatic  tissue.  Further,  certain 
groups  of  glands  for  some  inexplainable  reason  are  more  frequently 
attacked  than  others.  This  enlargement  bears  no  relation  to  cuta- 
neous or  other  lesions,  although  it  is  seen  more  often  during  the  first 
year  of  the  disease  than  later.  The  most  frequently  affected  glands 
are  those  of  the  neck,  especially  the  posterior  cervical,  the  occipital, 
and  the  epitrochlear.  The  axillary  glands  and  the  inguinal  glands 
if  not  primarily  involved,  sometimes  are  enlarged  independently 
of  other  lesions. 

This  adenitis  may  appear  before  any  cutaneous  lesions  are 
observed,  is  practically  always  noted  with  such  lesions,  and  may 
persist  for  some  time  following  the  healing  of  the  syphilodermata. 
The  glands  never  suppurate  except  when  complications  exist  and 


68  CLINICAL  HISTORY 

usually  disappear  with  resolution.  The  size  attained  by  the  lym- 
phatic glands  under  these  conditions  varies  from  1  or  2  mm.  in 
diameter,  and  scarcely  palpable,  to  2  or  3  cm.  and  easily  observed 
as  distinct  tumors.  While  usually  only  one  gland  is  involved,  two 
or  even  three  may  be  enlarged  and  may  be  connected  by  an 
indurated  cord. 

The  lymph  glands  rarely  may  be  the  seat  of  gummatous  formation. 
This  condition  usually  occurs  late  in  the  course  of  the  disease, 
but  may  be  observed  as  early  as  the  first  year.  Gummata  of  the 
lymphatic  glands  tend  to  soften  and  if  superficial  may  form  ulcers. 
Several  gummatous  glands  may  grow  together  by  the  development 
of  connective  tissue  and  form  large  masses. 

CUTANEOUS  LESIONS. 

The  syphilodermata,  which  are  the  most  striking  outward  mani- 
festations of  syphilis,  as  pointed  out  above,  may  assume  almost 
any  form  and  resemble  any  known  skin  disease.  For  example, 
the  pigmentary  syphiloderm  m.ay  resemble  vitiligo,  and  the  term 
vitiligoid  syphiloderm  or  syphilitic  leukoderma  often  is  applied. 
Such  terms  not  infrequently  are  misleading  and  should  be  dis- 
couraged. 

Macular  Syphiloderm. — The  most  frequent  form  of  the  macular 
syphiloderm  is  the  roseolar  which  is  also  the  most  common  of  all 
the  skin  manifestations  of  syphilis.  This  usually  is  observed  six 
to  seven  weeks  following  the  appearance  of  the  chancre,  although 
the  time  may  be  shorter  or  considerably  longer. 

The  roseolar  syphiloderm  in  the  majority  of  cases  begins  on  the 
upper  abdom.en,  spreads  to  the  thorax  and  later  may  involve  nearly 
the  entire  surface  of  the  body.  The  dorsal  surfaces  of  the  hands 
and  feet  usually  escape.  Occasionally  the  eruption  begins  on  the 
face,  being  most  prominent  about  the  nose,  mouth,  chin  and  especi- 
ally the  forehead.  This  syphiloderm  consists  of  variously  sized 
spots  which  usually  are  on  a  level  with  the  surrounding  skin  but 
may  be  slightly  elevated.  The  average  size  is  about  1  cm.  in 
diameter,  although  they  may  be  considerably  smaller  and  occasion- 
ally become  much  larger.  The  shape  is  round  or  oval  with  distinct 
or  irregular  outline.  At  first  the  color  is  a  pale  pink  or  a  reddish 
violet  which  disappears  on  pressure,  but  later  assumes  a  dark  red, 
coppery  tinge,  often  described  as  resembling  the  color  of  lean  ham. 
The  development  of  the  roseolar  eruption  may  be  very  sudden, 
sometimes  being  brought  out  by  violent  exertion  or  occasionally 
by  a  hot  bath. 

Often  the  spots  are  faint  in  color  and  escape  notice  until  the 
surface  of  the  body  is  exposed,  as  for  the  purpose  of  physical 


CUTANEOUS  LESIONS 


69 


examination.  The  number  of  the  lesions  varies  from  a  few  scattered 
spots  to  a  profuse  crowded  condition,  which  occupies  the  greater 
portion  of  the  skin,  leaving  a  comparatively  small  area  of  normal 
skin  between  the  macules.  Rarely  coalescence  takes  place.  The 
eruption  usually  persists  for  several  weeks  and  may  disappear 
quickly  or  gradually.  Ordinarily  there  is  little  or  no  desquamation, 
although  with  palmar  lesions  this  is  not  infrequent. 

The  annular  macular  syphiloderm  is  rare  and  generally  is  seen 
as  a  recurrence.  While  it  usually  appears  within  a  few  months 
following  the  chancre,  it  has  been  noted  as  late  as  four  or  five  years 
after  the  initial  lesion.    It  is,  as  the  name  implies,  of  ring-shaped 


Fig.  9. — Macular  {roseolar)  syphiloderm. 

outline  and,  as  a  rule,  is  limited  in  area  and  in  the  number  of  rings. 
A  concentric  arrangement  of  the  rings  is  occasionally  seen.  This 
eruption  is  most  frequently  found  on  the  neck,  shoulders,  and 
forearms. 

The  pigmentary  syphiloderm  has  been  the  subject  of  much  dis- 
cussion and  its  existence  as  a  distinct  syphilitic  eruption  has  been 
questioned.  Fox^  states  that  it  is  neither  pigmentary  nor  syphilitic, 
that  the  dark  recticulum  is  secondary,  and  the  whitish  macules 
develop" first  on  the  site  of  former  syphilitic  lesions.    There  seems 

1  Jour.  Cutan.  Dis.,  1913,  xxxi,  p.  224. 


70 


CLINICAL  HISTORY 


Fig.   10. — Macular  (roseolar)  syphiloderm. 


Fig.  11. — Pigmentary  (vitiligoid)  syphiloderm.     (Ormsby.) 


CUTANEOUS  LESIONS  71 

no  doubt,  however,  that  aside  from  the  pigmentation  of  the  skin 
following  certain  other  syphilodermata  there  occasionally  develops 
an  original  discoloration  of  the  skin  due  to  syphilis. 

According  to  Taylor^  three  varieties  of  the  pigmentary  syphil- 
oderm  are  seen  which  are  as  follows: 

1.  Spots  or  patches  of  various  sizes. 

2.  More  or  less  diffuse  pigmentation,  sooner  or  later  becoming 
the  seat  of  leukodermic  change  in  the  shape  of  small  retiform  spots 
which  gradually  increase  in  size. 

3.  A  so-called  marmoraceous  pigmentary  syphiloderm  formed  by 
an  abnormal  distribution  of  the  pigment  of  the  skin,  some  places 
becoming  whiter  than  normal  by  the  lack  or  crowding  out  of  pig- 
ment and  others  darker  by  the  abnormal  distribution  of  pigment. 

The  first  type  consisting  of  spots  or  patches  of  rounder  or  oval 
form  with  sometimes  irregular  edges,  varies  in  color  from  light  to 
dark  brown,  the  edges  of  the  spots  showing  the  darker  color.  The 
intervening  skin  is  usually  normal  in  color  but  appears  whiter, 
owing  to  the  pigmentation  of  the  spots.  The  pigmentation  may  last 
for  months,  after  which  it  may  slowly  fade  and  disappear.  Some- 
times areas  without  pigmentation  are  left  which  are  termed 
secondary  or  yseudoleukodervia  by  Taylor.  However,  as  a  rule,  the 
skin  returns  to  normal  after  the  disappearance  of  the  pigment. 

In  the  second  form  of  pigmentary  syphiloderm  described  by 
Taylor,  the  so-called  lace  or  retiform  variety,  which  is  the  most 
frequent,  the  sides  or  back  of  the  neck  either  slowly  or  rapidly 
become  discolored,  sometimes  extending  to  the  shoulders  or  trunk. 
The  color  is  described  as  that  of  cafe-au-lait  or  yellowish-brown. 
Gradually  whitish  spots  develop  in  the  pigmented  area,  beginning 
as  minute  specks  and  in  a  short  time  attaining  considerable  size  and 
presenting  round,  oval,  linear  or  irregular  shape.  The  white  spots 
may  actually  be  lighter  than  the  normal  skin  or  they  may  only 
appear  so  by  contrast  with  the  pigmented  areas.  As  the  white 
spots  increase  in  size  the  pigmented  areas  become  smaller  and  may 
eventually  consist  of  narrow  bands  which  cause  the  lesions  to  have 
the  appearance  of  lace,  the  white  spots  forming  the  interstices. 

The  third  form,  termed  marmoraceous  on  account  of  its  supposed 
resemblance  to  som.e  forms  of  marble,  appears  slowly,  and,  according 
to  Taylor,  only  on  the  sides  of  the  neck.  It  is  the  rarest  variety 
of  the  pigmentary  syphilodermata.  Spots  of  the  skin  of  varying 
size  and  shape  become  white,  while  the  skin  between  the  spots 
becomes  brown.  The  margins  are  hazy  and  indefinite.  There  is 
no  hyperpigmentation,  the  change  in  color  seeming  to  be  due  to 
irregular  distribution  of  the  normal  pigment.     After  a  variable 

1  The  Pathology  and  Treatment  of  Venereal   Diseases,  Philadelphia,  1895,  p.  638. 


72  CLINICAL  HISTORY 

period  of  time  the  lesions  slowly  disappear  and  the  skin  is  left  in  a 
normal  condition. 

The  pigmentary  syphilodermata  occur  at  varying  periods  follow- 
ing the  initial  lesion,  usually,  however,  from  about  the  sixth  month 
to  the  end  of  the  first  year.  In  one  case  seen  by  the  author  this 
manifestation  was  observed  eight  months  following  the  chancre 
of  the  left  labium  majus.    The  pigmentary  syphiloderm  may  be  the 


Fig.   12. — Papular  (lenticular)    syphiloderm.     (This  eruption  occurred  fifteen  years 

after  the  chancre.) 

only  syphilitic  lesion  present  or  it  may  occur  in  connection  with 
other  syphilodermata.  It  is  most  frequently  seen  in  females, 
males  being  rarely  affected  in  this  manner.  The  chief  regions 
involved  are  the  sides  and  back  of  the  neck,  rarely  the  face,  trunk, 
arms  and  legs. 

Papular  Syphiloderm. — This  variety  of  syphilitic  eruption  may 
follow  the  macular  syphiloderm,  the  latter  merging  into  the  papular 
variety  gradually,  so  that  the  term  maculopapular  syphiloderm 


CUTANEOUS  LESIONS 


73 


may  be  applied  with  perfect  propriety.  On  the  other  hand,  the 
papular  syphiloderm  may  appear  as  the  first  rash  of  the  disease. 
The  time  of  the  appearance  of  this  syphilitic  lesion  is  subject  to 
great  variations,  it  being  observed  sometimes  as  early  as  the  second 
or  third  month  or  as  late  as  several  years  following  the  initial 
lesion.  One  characteristic  of  the  papular  syphilodermata  is  their 
tendency  to  recurrence,  and  this  phenomenon  may  be  noted  under 
one  form  or  another  for  a  number  of  years.  The  author  has  recently 
had  under  his  care  a  caSe  in  which  a  lenticular  papular  eruption 
occurred  fifteen  years  following  the  chancre  (see  Fig.  12). 


Fig.  13. — Papular  (miliary)  syphiloderm. 

While  the  miliary  papular  syphiloderm  is  of  comparatively 
frequent  occurrence,  it  is  not  noted  as  often  as  the  lenticular  form. 
The  mihary  eruption  varies  in  size  from  a  pin-head  to  that  of  a 
French  pea,  is  usually  associated  with  the  hair  follicles  and  is 
therefore  sometimes  termed  follicular.  This  lesion  consists  of 
accuminate  or  rounded  projections,  solid  and  rough  to  the  touch, 
which  when  large  sometimes  show  a  slight  umbilication.  Frequently 
early  in  the  course  of  the  development  of  the  miliary  papular 
syphiloderm  there  is  a  tendency  shown  by  the  larger  lesions  to  form 


74 


CLINICAL  HISTORY 


minute  vesicles  at  the  summit  which  last  only  a  few  days  and  upon 
drying  show  an  epithelial  scale.  Occasionally  also  the  summit  is 
surrounded  by  a  small  pustule.  The  most  frequent  location  of  this 
syphiloderm  is  on  the  face,  neck,  shoulders,  back,  arms,  and  thighs. 
The  separate  lesions  are  often  closely  crowded  and  tend  to  form 
groups  in  circles  or  semicircles  with  10  to  40  papules  in  a  group, 
while  the  intervening  skin  is  normal.  This  is  especially  true  of  the 
smaller  form  and  in  relapses  or  when  the  lesion  appears  late.  It  is 
frequently  noted  that  the  trunk  is  the  seat  of  small  papules,  while 
at  the  same  time  larger  papules  are  found  on  other  portions  of  the 
bodv. 


^B" 

. 

_ 

■  ■■'■"fi* 

') 

if^HHl^K^;  ., 

Fig.   14. — Papular  (le?iticular)  syphiloderm. 

The  color  of  the  miliary  papular  syphiloderm  is  at  first  a  bright 
red  and  later  fading  to  a  dark  brownish  or  violaceous  red.  The 
course  of  this  lesion  tends  to  be  chronic,  lasting  from  a  few  weeks 
to  several  months  and  perhaps  disappearing  spontaneously,  the 
color  becoming  duller  and  more  somber.  A  bluish  or  brownish-red 
stain  may  persist  for  some  time,  but  no  scarring  is  noted  except 
when  the  papule  has  contained  a  pustule.  It  is  often  noted  that 
fresh  papules  develop  scattered  among  the  original  lesions. 

The  lenticular  or  flat  papular  syphiloderm  is,  next  to  the  reseolar 
syphiloderm,   the  most  frequently  noted  of  the   skin  lesions   of 


CUTANEOUS  LESIONS 


75 


syphilis.  The  papules  are  round  or  oval,  flattened,  slightly  convex, 
raised  but  little  above  the  surrounding  skin,  have  sharply  defined 
borders  and  show  some  infiltration.  They  vary  in  size  from  that 
of  a  pea  to  a  large  bean  or  even  larger.  When  very  large  this 
type  of  syphiloderm  is  sometimes  termed  nuvmiular,  and  is  occasion- 
ally seen  as  large  as  a  silver  half-dollar  or  larger.  The  color  is  a 
dull  brownish-red.  The  syphiloderm  is  distributed  very  extensively 
on  the  forehead,  back  of  the  neck,  shoulders,  scalp,  arms  and  legs, 
especially  the  flexor  aspect.    The  palms  of  the  hands  and  soles  of 


Fig.   15. — Papular  (h'/UicuInr)  syphiloderm. 

the  feet  are  usually  free  from  the  eruption.  These  papules  are 
usually  not  so  abundant  as  the  miliary  type  and  are  less  frequently 
found  with  other  varieties  of  syphilodermata,  although  sometimes 
a  few  macular  and  pustular  lesions  may  be  seen. 

The  development  of  the  lenticular  papular  syphiloderm  is  usuafly 
slow  and  often  comes  in  successive  "crops."  As  the  papule  develops 
the  surface  undergoes  more  or  less  change,  the  epidermis  becoming 
red  and  shiny  and  later  the  centre  desquamates,  the  papules  gradu- 
ally becoming  flatter  and  disappearing  by  resolution.  There  is 
usually  some  brownish  or  grayish  pigmentation  left  which  is  very 


76  CLINICAL  HISTORY 

persistent.     There  is  little  tendency  to  grouping  and  ordinarily 
none  to  coalesce. 

A  case  which  has  recently  come  under  the  care  of  the  author  is  a 
striking  example  of  this  type  of  eruption  (see  Fig.  16).  It  will  be 
observed  that  almost  the  entire  face  is  covered  with  a  continuous 
dark  red  eruption,  only  a  few  spots  of  normal  skin  remaining, 
while  small  and  large  spots  cover  a  large  portion  of  the  remaining 
cutaneous  surface. 


Fig.  16. — Papular  (nummular)  syphiloderm.     (Note  that  the  face  is  almost  com- 
pletely covered  by  the  confluence  of  the  eruptions.) 

In  certain  cases,  especially  in  negroes,  there  is  a  tendency  to  ring 
formation,  the  eruption  appearing  as  complete  or  partial  circles, 
and  is  given  the  term  annular  or  circinate  syphiloderm.  This 
condition  is  brought  about,  according  to  Hazen,^  in  a  number  of 
different  ways  and  may  develop  from  the  miliary  lesions  as  well 

1  Jour.  Cutan.  Dis.,  1913,  xxxi,  p.  148. 


CUTANEOUS  LESIONS 


77 


as  from  the  lenticular.  As  it  probably  always  develops  from  one 
or  the  other  of  the  papular  syphilodermata  it  should  not  be  con- 
sidered as  a  distinct  variety.  The  papules  may  be  grouped  in  a 
circle,  the  central  ones  rapidly  disappearing  and  the  peripheral 
ones  coalescing  more  or  less  and  forming  the  circular  lesions.  Or 
the  annular  lesions  may  develop  from  a  single  papule  which  first 


Fig.  17. — Papular  (annular)  syphiloderm. 


spreads,  after  which  the  border  becomes  slightly  raised  and  absorp- 
tion takes  place  either  in  the  centre  or  more  frequently  just  within 
the  outer  rim.  Or  finally  a  number  of  papules  may  form  a  ring 
without  any  lesions  in  the  centre. 

Single  miliary  lesions  rarely  develop  into  the  annular  syphiloderm; 
the  same  is  true  of  the  smaller  lenticular  lesions  but  the  larger  ones 


78  CLINICAL  HISTORY 

quite  frequently  do  so.  The  size  of  the  annular  lesion  is  usually 
about  1  or  2  cm.  in  diameter,  although  it  may  be  considerably  larger. 
Several  may  coalesce,  forming  fantastic  patterns,  and  not  infre- 
quently two  or  more  may  be  concentric.  The  number  varies 
from  one  to  a  hundred  or  more.  The  most  frequent  location  of  this 
syphiloderm  is  on  the  face  but  may  be  seen  on  the  neck,  body  or 
limbs.  It  may  be  the  only  type  of  lesion  present  or  may  be  accom- 
panied by  others. 

The  lenticular  papular  syphiloderm  quite  frequently  shows  a 
tendency  to  marked  desquamation  instead  of  the  slight  scaling 
usually  noted,  which  has  led  to  the  term  pajnilosquamous  syphilo- 


FiG.   18. — Papular  (annular)  syphiloderm  {concentric). 

derm.  On  account  of  the  resemblance  of  this  condition  to  psoriasis 
it  has  erroneously  been  designated  syi^hilitic  psoriasis.  The  papules 
at  first  usually  become  slightly  less  elevfited  and  an  accumulation 
of  epidermic  scales  takes  place.  This  scaling  may  be  very  slight 
and  the  scales  thin  and  wrinkled,  or  it  may  be  very  marked,  the 
scales  being  dry,  of  a  dirty  grayish  or  brownish  color,  thick  and 
usually  friable.  Occasionally  they  are  hard  and  horny  and  adherent. 
When  removed  the  papule  is  seen  beneath,  flat  and  of  a  dark  red 
color.  Pruritis  is  rare  and  never  marked  except  in  the  negro. 
The  papules  which  appear  late  in  the  disease  or  as  recurrences  are 
more  likely  to  exhibit  this  tendency  of  desquamation.  Also  those 
of  certain  localities  as  on  the  face,  along  the  eyebrows  and  chin. 


CUTANEOUS  LESIONS 


79 


and  on  the  palms  and  soles  show  a  special  predisposition  to  this 
condition. 

While  the  palms  of  the  hands  and  the  soles  of  the  feet  may  be 
the  seat  of  most  of  the  syphilodermata,  when  they  are  attacked  by 
the  papulosquamous  form  the  terms  palmar  and  plantar  syphiloderm 
are  applied.  Although  these  lesions  are  papular  in  character,  they 
present  certain  peculiarities  which  account  for  the  special  terms. 
These  peculiarities  are  due  to  the  thickness  of  the  epidermis  of 
these  regions  and  the  firm  adherence  of  the  dermis  to  the  underlying 
fascia.  The  papules  are  flat  with  scarcely  any  elevation  above  the 
surrounding  surface,  although  there  is  distinct  infiltration.  At 
first  they  appear  more  as  macules  than  as  papules,  are  of  a  dull 
red  or  yellowish-red  color  and  vary  in  size  from  that  of  a  pea  to  the 


Fig.  19. — Papular  {squamous)  syphiloderm  (palmar). 


diameter  of  a  silver  ten-cent  piece.  Later  the  epidermis  becomes 
partially  separated,  the  color  being  a  dirty  gray,  while  beneath, 
the  underlying  lesion  retains  the  usual  red  color.  The  papules 
'usually  first  develop  in  the  centre  of  the  palms  or  soles  and  may 
extend  by  creeping,  with  an  elevated  border,  to  the  fingers  and  toes 
or  even  to  the  dorsal  surfaces.  There  is  also  a  tendency  to  coalesce, 
the  whole  surface  of  the  palm  or  sole  being  covered  by  the  lesion. 

Sometimes  the  natural  folds  or  furrows  of  the  skin  of  these 
regions  become  the  seat  of  deep  cracks  or  fissures  which  may  become 
exceedingly  painful  and  refractory. 

While  this  type  of  eruption  is  more  frequently  observed  on  the 
palms  of  the  hands,  it  is  sometimes  seen  on  the  soles  of  the  feet 
as  well  and  occasionally  on  the  latter  alone.    Rarely  only  one  hand 


80  CLINICAL  HISTORY     . 

or  one  foot  is  attacked.  This  type  of  lesion  appearing  late  in  the 
course  of  the  disease  is  often  most  resistant  to  treatment,  and  even 
when  observed  early  with  other  syphilodermata,  it  is  usually  less 
am.enable  to  therapy  than  the  concomitant  lesions. 

When  a  lenticular  papule,  instead  of  desquamating,  presents  a 
more  or  less  moist  appearance,  the  term  moist  papular  syphiloderm 
is  applied.  This  type  of  lesion  is  usually  met  with  early  in  the 
disease  and  may  be  observed  with  other  types  or  alone.  However, 
if  not  treated,  it  may  persist  almost  indefinitely  and  has  been 


Fig.  20. — Papular  {squamous)  syphiloderm  (plantar). 

observed  as  a  recurrence  as  late  as  twenty  to  thirty  years  following 
the  chancre.  The  moist  papule  usually  begins  as  a  flattened  ele- 
vation, circular,  and  varying  in  diameter  from  2  or  3  mm.  to  1  cm. 
The  reason  that  certain  papules  develop  into  the  moist  type  is  to 
be  found  largely  in  the  location.  The  thinness  of  the  skin,  the 
apposition  of  contiguous  surfaces,  the  warmth  and  the  moisture 
from  perspiration  all  act  as  contributing  factors.  The  most  frequent 
location  of  the  moist  papule  is  about  the  anus  and  genitalia,  especi- 
ally in  women.    Not  infrequently  in  the  latter  this  eruption  may  be 


CUTANEOUS  LESIONS 


81 


the  only  skin  lesion  developing  throughout  the  entire  course  of  the 
disease.  The  corner  of  the  mouth,  the  nasolabial  fold,  the  axillae, 
the  skin  beneath  the  breasts,  the  interdigital  spaces  and  the  skin 
around  the  umbilicus  may  be  the  seat  of  this  lesion. 


Fig.  21. — Papular  (vegetating)  syphiloderm. 


Fig.  22. — Vegetating  condylomata  of  the  vulva  and  anus.     (Ormsby.) 


As  stated,  the  moist  papule  begins  as  a  flattened,  elevated  lesion 
which,  instead  of  desquamating,  becomes  soft  and  the  surface 
6 


82 


CLINICAL  HISTORY 


presents  a  grayish  or  brownish-gray,  easily  detached,  mucoid 
pellicle,  composed  of  macerated  epidermis.  Sometimes  large,  flat 
patches  are  formed  by  the  coalescence  of  two  or  more  lesions. 
Not  infrequently  these  papules  may  become  ulcerated.  The  moist 
papular  syphiloderm  instead  of  becoming  flat  occasionally  hyper- 
trophies and  becomes  warty  or  papillomatous.  Several  lesions 
coalesce  and  a  large  cauliflower  mass,  surrounding  the  anus,  or,  in 
the  female,  the  vulva,  may  develop,  and  is  often  termed  vegetating 
syphiloderm  or  condyloma.  These  lesions  may  occur  in  other 
localities,  as  for  example,  the  nose.  (Fig.  21.)  It  is  accompanied 
by  more  or  less  mucoid  secretion  and  unless  strict  cleanliness  is 
observed  a  most  foul  odor  develops. 


Fig.  23.— Lenticular  {moist)  papular  syphiloderm.     (Condylomata.) 

These  lesions  are  usually  very  amenable  to  treatment,  but 
occasionally  they  break  down  spontaneously  by  a  process  of  ulcera- 
tion. This  latter  process,  however,  does  not,  as  a  rule,  involve  the 
skin  upon  which  the  lesions  are  located,  so  there  is  little  or  no  loss 
of  tissue  when  cicatrization  takes  place. 

Vesicular  Syphiloderm. — Fox^  flatly  denies  the  existence  of  a 
cutaneous  lesion  in  syphilis  worthy  of  the  name  vesicular.  Morrow^ 
states  that  vesicles  are  sometimes  formed  on  erythematopapular 
lesions  due  to  the  intensity  of  the  inflammatory  process,  but  con- 
siders them  as  an  accidental  or  accessory  phenomenon  and  of 


1  Jour.  Cut.  Dis.,  1913,  xxxi,  p.  224. 

2  A  System  of  Genito-urinary  Diseases,  Syphilology  and  Dermatology,  New  York, 
1898,  ii,  p.  146. 


CUTANEOUS  LESIONS  83 

limited  duration.  He  therefore  does  not  think  that  this  type  of 
lesion  should  be  elevated  to  the  dignity  of  a  separate  class. 

On  the  other  hand,  Duhring^  states  that  while  the  majority  of 
so-called  syphilitic  vesicles  may  more  properly  be  viewed  as  early 
pustules,  occasionally  lesions  are  observed  that  present  throughout 
their  course  characters  which  entitle  them  to  be  termed  vesicular. 
This  author  states  that  Bassereau  and  also  Hardy  have  described 
these  lesions  at  length  and  that  they  are  of  various  size,  from  pin- 
head  to  split-pea,  more  or  less  acuminated,  disseminated  or  grouped, 
flat  or  semiglobular  with  or  without  umbilication.  They  always 
occur  within  the  first  year,  usually  within  the  first  six  months  and 
are  generally  associated  with  other  lesions. 

Dennie^  describes  the  lesions  of  one  case  observed  by  him  as 
being  1  to  4  mm.  in  diameter,  sparsely  scattered  over  the  back 
and  flanks,  elevated  considerably  above  the  smrounding  cutaneous 
surface  and  appearing  t^ranslucent  and  tense  with  fluid  as  if  quite 
deeply  situated. 

In  quite  an  extensive  observation  of  syphilitics  in  Hot  Springs 
the  author  has  not  seen  the  vesicular  syphiloderm  and  on  question- 
ing a  number  of  physicians  who  have  practised  here,  some  of  them  as 
long  as  thirty  years,  he  has  been  unable  to  learn  pf  a  single"  case 
in  which  the  diagnosis  was  undoubted. 

Bullous  Syjghiloderm.— This  variety  of  syphilitic  lesion  is  also 
very  rare  in  the  acquired  form  of  the  disease  and  its  existence 
is  denied  by  some  authorities.  Fox^  states  that  it  is  never  seen 
when  the  patient  is  not  suffering  from  iodism,  and  Morrow^  says 
that  it  cannot  be  considered  as  a  distinct  type,  as  the  lesions  which 
begin  as  bullse  rapidly  undergo  a  purulent  transformation.  This 
probably  is  usually  the  case  but  undoubtedly  sometimes  bullous 
lesions  develop  which  do  not  become  pustular.  They  are,  as  a 
rule,  developed  late  in  the  course  of  the  disease  and  generally 
in  individuals  of  markedly  lowered  vitality.  They  are  discrete, 
disseminated,  round  or  oval  blebs,  pea-  to  walnut-sized  and  sur- 
rounded by  a  dark  red  areola.  They  either  ruptm'e  or  collapse 
without  rupturing  and  dry  to  brownish  or  greenish  crusts.  Beneath 
the  crusts  are  erosions  or  ulcers  which  upon  healing  leave  pigmented 
cicatrices.  -  This  type  of  lesion  is  usually  rather  amenable  to 
treatment. 

Pustular  Syphiloderm. — This  variety  of  syphilitic  lesion  may 
develop  from  a  previous  macular  or  papular  eruption  or  it  may 
appear  as  the  first  skin  manifestation  of  the  disease.  It  is  rare  to 
see  all  of  the  lesions  in  any  one  case  of  the  pustular  variety,  papules 

1  Diseases  of  the  Skin,  Philadelphia,  1882,  p.  519. 

2  Jour.  Cut.  Dis.,  1915,  xxxiii,  p.  509. 

*  Loc.  cit.  *  Loc  cit. 


84  ■  CLINICAL  HISTORY 

also  being  observed  in  greater  or  less  profusion.  This  syphiloderm 
is  most  frequently  seen  in  individuals  of  lowered  vitality  whose 
general  health  is  not  good.  It  is,  however,  undoubtedly  caused, 
not  by  the  Treponema  pallidum  alone,  but  secondary  pyogenic 
organisms  are  responsible  to  a  large  extent  for  its  development. 
While  it  usually  appears  within  the  first  six  or  eight  months  following 
the  chancre,  it  may  be  seen,  especially  as  a  recurrence,  much  later 
in  the  course  of  the  disease.  This  variety  of  syphiloderm  is  a 
much  less  frequently  observed  lesion  than  either  the  macular  or 
papular  varieties. 

The  acuminate  pustular  syphiloderm  occurs,  as  the  name  implies, 
as  pointed  or  rounded  pustules.  The  size  varies  from  that  of  a 
pin-head  (small)  to  the  size   of  a  pea  (large).     The   small-sized 


Fig.  24. — Biillous  syphiloderm  showing  bullae  and  crusts. 

eruptions  are  often  referred  to  as  miliary  and  the  large-sized  as 
acneiform  or  varioliform.  The  small  size  are  always,  and  the  large 
size,  sometimes,  connected  with  the  hair  follicles.  When  the  lesions 
begin  as  papules  there  is  usually  a  pinkish-red  to  dark  red  base  which 
may  continue  as  such  or  be  transformed  into  a  part  of  the  pustule. 
Even  the  small-sized  pustules  sometimes  show  a  slight  depression 
of  the  summit,  while  this  umbilication  is  more  frequently  observed 
in  the  larger  lesions. 

Both  sizes  are  usually  quite  abundant  and  may  be  distributed 
over  almost  the  entire  cutaneous  surface.  There  is,  however,  a 
tendency  to  form  groups,  especially  when  appearing  as  recurrences 
when,  as  a  rule,  also  the  eruption  is  more  scanty.  The  development 
of  the  acuminate  pustular  syphiloderm  is  sometimes  rapid,  but 


CUTANEOUS  LESIONS 


85 


usually  is  more  or  less  gradual,  lasting  several  weeks,  showing  little 
disposition  to  spontaneous  cure.  The  pustules  dry  to  crusts  which 
fall  off  and  leave  a  fringe-like  exfoliation  of  epidermis  around  the 
base  which  has  been  termed  the  "collaret."  In  the  larger  lesions 
a  superficially  eroded  base  is  found  beneath  the  crusts  when  first 
formed.  The  small  lesions  may  heal  with  no  trace  left  behind  but  a 
slight  pigmentation  or  they  may  leave  small  pits,  while  the  larger 
lesions  occasionally  leave  atrophic  thinning  with  slight  scarring. 

The  large  and  small,  flat  pustular  syphilodermata  resemble  each 
other  in  many  respects  but  in  certain  other  respects  they  are  so 
markedly  different  that  it  is  thought  best  to  describe  them  under 
separate  headings. 


Fig.  25. — Papulopustular  syphiloderm. 

The  small,  fiat,  imstular  syphilodern,  often  called  impetigoform,  is  a 
rounded  or  oblong,  flattened,  pustular  eruption,  varying  in  size  from 
2  or  3  mm.  to  1  cm.  in  diameter.  It  is  usually  superficially  located  but 
rarely  is  deep.  It  is  found  particularly  on  the  hairy  parts,  the  scalp, 
the  pubes,  in  men  on  the  chin,  but  is  also  seen  in  other  localities, 
as  the  forehead,  nasolabial  fold,  and  rarely  on  the  abdomen  or  back. 
The  lesion  is  usually  observed  as  a  discrete  eruption  but  irregular 
grouping  sometimes  is  seen,  while  in  certain  localities,  especially 
the  scalp,  coalescence  is  not  uncommon.    The  development  of  the 


86 


CLINICAL  HISTORY 


small,  flat  pustular  syphiloderm  is  usually  somewhat  rapid  and  soon 
dries  into  a  thick,  dirty  yellow  or  brownish  crust  which  may  or  may 
not  be  adherent.  Beneath  the  crust,  which  sometimes  does  not 
completely  cover  the  base,  is  seen  a  slight  ulcerated  area,  which 
upon  healing,  leaves  little  scarring,  but  a  pigmented  spot  may  persist 
for  considerable  time.  As  a  rule  this  type  of  lesion  is  readily 
amenable  to  treatment,  although  if  very  extensive  and  the  ulceration 
deep  may  be  difficult  to  cure. 


Fig.  26. — Pustular  (acuminate)  syphiloderm. 

The  large,  fiat  pustular  syphiloderm  is  observed  as  a  superficial 
or  as  a  deep  lesion,  the  latter  being  seen  later  in  the  disease  and 
is  rarer.  The  superficial  lesion  does  not  differ  materially  from  the 
small,  flat  pustular  syphiloderm  except  in  size  and  in  the  usual 


CUTANEOUS  LESIONS  87 

location  which  is  on  the  lower  extremities,  neck,  inguinal  and 
gluteal  regions  and  rarely  on  the  trunk.  These  pustules  dry  to 
yellowish  brown  or  brownish  crusts,  are  more  or  less  adherent, 
and  when  removed  leave  an  ulcerated  base  with  an  infiltrated, 
dark  red  border.  A  crust  may  reform  several  times  before  the 
process  of  healing  is  complete.  Occasionally  the  crusts  form  so 
rapidly  that  the  term  inistulocrustaceous  syphiloderm  is  applied. 


Fig.  27. — Pustular  {fiat)  syphiloderm. 

The  deep-seated,  flat,  pustular  syphiloderm  is  usually  a  late 
manifestation  of  the  disease,  but  has  been  noted  during  the  early 
course  in  severe  or  so-called  malignant  syphilis.  In  this  type  of 
lesion  the  crust  is  thicker  and  of  a  darker  color,  even  a  brownish- 
black,  with  sometimes  a  greenish  tinge.     Upon  removal  of  the 


88  CLINICAL  HISTORY 

crust  a  punched-out  ulcerative  area  is  revealed,  which  is  grayish, 
dark  brown  or  bright  red  in  color  and  secretes  a  purulent  bloody 
fluid  which  in  a  short  time  forms  another  crust.  Or  the  crust 
formation  may  go  on  without  removal  of  the  superficial  crust  and 
several  layers  be  formed,  one  beneath  the  other,  until  a  laminated 
shell-like  lesion,  which  is  termed  nqna,  is  observed.  Sometimes  the 
crust  is  slightly  smaller  than  the  underlying  ulcer  and  has  the 
appearance  of  having  been  "cut  to  fit." 


Fig.  28. — Pustular  crustaceous  syphiloderm. 


The  most  frequent  location  of  this  type  of  lesion  is  on  the  face, 
arms,  back,  and  shoulders.  It  may  be  rather  abundant  but  rarely  is 
profuse.  Sometimes  two  or  more  lesions  may  coalesce,  forming 
large  crustacous  areas.  The  healing  process  is  usually  slow.  The 
floor  of  the  ulcer  clears  up  and  is  filled  with  healthy  granulations; 
however,  the  crust  may  persist  until  complete  healing  has  taken 


CUTANEOUS  LESIONS 


89 


place.  A  red,  depressed  scar  is  left  which  is  surrounded  by  a 
coppery  areola  and  persists  for  a  long  time.  It  may  later  fade  to  a 
dead  white  color.  It  has  been  observed  that  extensive  pustular 
syphilodermata  frequently  follow  severe  chancres. 


Fig.  29. — Pustular  syphiloderm  (rupia). 


Fig.  30. — Nodular  (serpiginous)  syphiloderm. 

Nodular  Syphiloderm. — ^This  type  of  syphilitic  lesion  is,  as  a  rule,  a 
comparatively  late  manifestation  of  the  disease,  but  it  may  develop 
within  the  first  year  when  it  usually  is  associated  with  the  papular 


90 


CLINICAL  HISTORY 


syphiloderm  or  the  lesion  may  partake  more  of  a  papular  nature 
and  the  condition  is  spoken  of  as  [japulonodular.  The  true  nodular 
or  tMhercular  syphiloderm  consists  of  a  firm,  circum.scribed,  more 
or  less  elevated  lesion,  which  may  involve  the  whole  thickness  of  the 
skin.  It  is  of  a  reddish-brown  or  copper  color  and  varies  in  size 
from  a  pea  to  a  good-sized  hazel  nut.  The  surface  is  sometimes 
smooth  and  glistening  or  it  may  be  covered  by  a  thin  scale  of 
exfoliating  epitheliLim.  This  type  of  syphiloderm  may  develop  on 
any  portion  of  the  body,  but  it  is  most  frequently  seen  on  the  head 


Fig.  31. — Extensive  nodular  (sorpiginous)  syphiloderm. 

and  face,  also  on  the  back  of  the  neck  and  shoulders,  the  extensor 
surfaces  of  the  joints  and  the  buttocks.  It  may  be  generalized 
or  it  may  occur  singly  or  in  groups.  The  coalescence  of  several 
nodules  may  form  a  circinate  or  serpiginous  lesion  which  terms  have 
been  applied.  The  development  and  retrogression  of  the  nodular 
syphiloderm  is  usually  chronic  and  as  new  lesions  appear  the  duration 
of  the  condition  may  be  months  or  even  years.  The  termination 
is  either  by  absorption,  exfoliation,  pustulation  or  ulceration. 
When  absorption  takes  place  a  brownish  pigmentation  is  left.    When 


CUTANEOUS  LESIONS  91 

exfoliation  is  excessive  the  terms  tuherculosquamous  is  applied, 
and  if  a  pustule  is  developed  in  the  lesion,  as  rarely  occurs,  it  is 
called  tuber culopustular.  However,  ulceration  is  the  usual  termina- 
tion of  the  nodular  syphiloderm.  The  lesion  becomes  soft  in  the 
centre,  breaks  down  and  an  open  ulcer  results.  This  may  be 
superficial  or  deep  and  crusting  usually  occurs.  The  ulcer  has 
a  punched-out  appearance  with  sharp-cut  edges  and  is  either  round 
or  crescentic  in  shape.    The  condition  may  be  progressive,  either  by 


Nodular  syphiloderm  (confluent). 


the  extension  of  a  single  ulcer,  or  by  the  confluence  of  two  or  more, 
and  wide  areas  may  be  affected.  Upon  healing  there  is  a  more  or 
less  irregular  reddish  cicatrix,  which  eventually  assumes  a  shining 
white  color  and  is  depressed  according  to  the  depth  of  the  lesion. 
This  type  of  lesion  is,  as  a  ride,  quite  amenable  to  treatment. 

Gummatous  Syphiloderm. — ^This  variety  of  syphilitic  lesion  is 
usually  the  latest  of  the  skin  manifestations  of  the  disease  to 
develop.    As  a  rule  it  does  not  occur  before  the  third  or  fourth 


92  CLINICAL  HISTORY 

year  following  the  initial  lesion  but  may  be  as  late  as  the  twentieth, 
thirtieth  or  even  fortieth  year  (Morrow).  On  the  other  hand, 
gummata  of  the  skin  have  been  noted  within  a  few  months  following 
the  chancre. 

The  essential  difference  between  the  gummatous  and  the  nodular 
syphilodermata  is  that  the  former  is  subdermal  in  origin  while  the 
later  is  intradermal.    A  gummatous  syphiloderm  first  appears  as  a 


Fig.  33. — Nodular  syphiloderm  (squamous). 

small  nodule  beneath  the  skin,  gradually  increasing  in  size,  stretch- 
ing the  skin  and  changing  its  color  to  a  dull  red.  The  growth  may 
be  slow  or  rapid  until  the  size  of  a  walnut  or  larger  is  attained. 
While  at  first  hard  and  firm,  it  usually  soon  becomes  necrotic  and 
soft,  owing  to  the  paucity  of  bloodvessels,  the  centre  breaks  down 
and  a  deep,  punched-out  ulcer  is  formed.  It  may,  however,  rarely 
resolve  without  ulceration.  If,  as  often  occurs,  instead  of  developing 
as  a  circumscribed  tumor  the  gumma  becomes  diffuse,  a  consider- 


CUTANEOUS  LESIONS 


93 


./sr'.« 

k^l 

^^tta^Mh...                  ^H 

^^^^^^^^•*  ^^^^H^HRHpiP 

^^j^H 

^1 

Hfetti 

^^H 

Fig.  34. — Nodular  syphiloderm  (ulcerating). 


Fig.  35. — Gummatous  syphiloderm. 


94 


CLINICAL  HISTORY 


able  area  may  be  affected  from  the  beginning.  The  skin  over  the 
lesion  is  at  first  pinkish  but  later  becomes  a  dull  red.  Ulceration 
usually  takes  place  in  several  places  and  soon  the  entire  area  may 
be  converted  into  an  ulcerating  lesion.  The  edges  of  the  ulcer 
are  usually  straight  and  sharp-cut,  but  may  be  slightly  sloping. 


Fig.  36. — Gummatous  syphiloderm  {ulcerating). 

While  no  part  of  the  cutaneous  surface  of  the  body  is  immune  to 
syphilitic  gummata  the  lower  extremities  are  most  frequently 
attacked. 

Sometimes  gummatous  syphilodermata  upon  ulceration  penetrate 
the  underlying  structures  and  great  destruction  of  tissue  follows. 


Fig.  37. — Gummatou?  syphiloderm  (ulcerating). 


On  the  other  hand,  the  lesion  may  be  comparatively  superficial,  be 
small,  slow  of  development,  with  little  or  no  tendency  to  ulceration. 
Such  lesions  not  infrequently  appear  on  the  penis  and  have  undoubt- 
edly been  mistaken  for  chancres.    (The  so-called  chancre  redux.) 


SYPHILIS  OF  THE  APPENDAGES  OF   THE  SKIN  95 

This  type  of  lesion  shows  Uttle  or  no  tendency  to  spontaneous 
healing  but  upon  treatment  usually  improvement  is  prompt.  There 
is  left  a  dark  red  scar  of  more  or  less  depth,  depending  upon  the 
depth  of  the  ulceration,  which  eventually  becomes  white  in  the 
centre  but  permanently  pigmented  at  the  periphery. 


SYPHILIS  OF  THE  APPENDAGES  OF  THE  SKIN. 

Hair. — Alopecia. — The  loss  of  hair  due  to  syphilis  is  a  well-known 
symptom  of  the  disease.  It  occurs  most  frequently  during  the 
jBrst  year  following  infection,  generally  soon  after  the  first 
cutaneous  manifestation.  It  may,  however,  be  seen  much  later; 
in  fact  may  follow  any  of  the  syphilodermata  which  have  attacked 
the  portion  of  the  body  covered  by  hair.  The  alopecia  following  the 
syphilodermata  is  due  to  interference  with  the  nutrition  of  the 
hair,  and  its  extent  depends  upon  the  extent  of  the  lesion.  On  the 
other  hand,  alopecia  may  occur  independently  of  the  syphilodermata 
and  varies  from  the  falling  of  a  few  hairs  of  the  head  to  complete 
alopecia  of  the  entire  body.  These  extreme  cases  are  exceedingly 
rare,  the  process  visually  being  limited  to  the  scalp.  Preceding 
the  falling  of  the  hairs  they  usually  lose  their  normal  lustre  and 
become  stiff,  dry,  and  wiry.  This  latter  condition  may  not  occur 
and  the  alopecia  is  the  only  symptom  observed.  The  hair  may  come 
out  in  patches  or  there  may  be  a  general  thinning.  The  loss  of  the 
hair  of  the  eyebrows  is  occasionally  noted,  especially  in  women. 
CorniP  states  that  the  loss  of  the  hair  of  the  eyebrows  in  spots  is  an 
almost  pathognomonic  sign  of  syphilis.  Alopecia  of  the  genitals, 
axillae  and  beard  also  occur  but  comparatively  rarely. 

The  loss  of  hair  due  to  the  presence  of  the  syphilodermata  is 
usually  permanent,  while  that  occurring  independently  of  the  skin 
manifestations  is  generally'  temporary,  the  hair  growing  back  upon 
the  institution  of  proper  treatment.  The  pathogenesis  of  the  latter 
type  of  alopecia  is  not  definitely  settled.  Dennie^  is  of  the  opinion 
that  it  is  not  directly  due  to  the  activity  of  the  treponemata  but  to 
the  pressure  of  the  infiltrating  substances. 

As  stated  above,  complete  syphilitic  alopecia  is  unusual.  It  is  not 
mentioned  by  most  text-books  or  is  dismissed  with  the  statement 
tha't  it  is  a  rare  condition. 

Abraham  and  Davis^  state  that  "more  cases  than  one"  of  complete 
syphilitic  alopecia  have  come  under  their  notice. 

Chambers  presented  a  case  before  the  Toronto  Clinical  Society, 

1  Syphilis,  American  edition,  Philadelphia,  1882,  p.  185. 

2  Jour.  Cut.  Dis.,  1915,  xxxiii,  p.  509. 

3  Power  and  Murphy:  System  of  Syphilis,  London,  1910,  v,  p.  100, 


96 


CLINICAL  HISTORY 


November  14,  1900.^  His  patient  was  a  female,  aged  twenty  years, 
in  whom  the  hair  began  to  fall  at  five,  and  again  at  twelve.  At  the 
age  of  eighteen  she  was  treated  for  interstitial  keratitis.  At  the 
time  of  presentation  there  were  but  two  hairs  on  the  body,  these 
being  located  on  the  anterior  portion  of  the  scalp. 

The  author  reported  the  following  case  in  1916:^  J.  F.,  male, 
aged  twenty-three  years;  Jew;  printer. 

Admitted  to  the  Leo  N.  Levy  Memorial  Hospital,  October  2, 
1914. 

Family  History. — Mother  died  after  parturition.  Father,  brothers 
and  sisters,  negative.    No  history  of  baldness  in  family. 


Fig.  38. 


-Alopecia  (early  form).     (Note  line  where  head  has  been  shaved  to  stimu- 
late growth  of  hair.) 


Past  History. — Negative. 

Present  Hlness. — Chancre,  May,  1912.  The  hair  of  the  eyebrows 
began  to  fall  out  two  weeks  after  the  appearance  of  the  chancre, 
the  right  side  being  first  affected.  Following  this  the  hair  of  other 
regions  began  to  fall  out,  and  in  two  months  the  body  was  entirely 
denuded. 

Three  weeks  following  the  appearance  of  the  chancre  the  mouth 
was  sore,  and  a  rash  appeared  on  the  abdomen,  back  and  left  fore- 
arm.   At  this  time  the  Wassermann  reaction  was  strongly  positive. 

One  week  later  he  received  an  intravenous  injection  of  salvarsan 
(dosage  not  known)  and  two  more  doses  at  weekly  intervals. 
Following  the  second  dose  he  had  fever  for  four  days. 


1  Jour.  Am.  Med.  Assn.,  1901,  xxxvi,  p.  57. 

2  Thompson:  Ibid.,  1916,  Ixvi,  p.  1303. 


SYPHILIS  OF  THE  APPENDAGES  OF  THE  SKIN  97 

The  patient  came  to  Hot  Springs,  in  September,  1913,  at  which 
time  he  complained  of  headache,  which  was  worse  at  night. 

He  then  received  injections  of  mercury  on  alternate  days  for  two 
weeks  (dosage  and  salt  not  known)  and  4  ounces  of  mercurial 
ointment  by  inunctions.  Potassium  iodide  was  administered  by 
mouth  up  to  150  grains  per  day  for  two  weeks. 

From  that  time  until  admission  to  the  hospital  no  treatment  was 
administered.  At  the  time  of  admission  the  patient  complained  of 
insomnia  and  nervousness. 

Examination. — The  most  striking  feature  of  this  case  is  the 
absolutely  complete  alopecia,  there  not  being  a  single  hair  on  the 
entire  body. 


«i 

Vf :  ;■'■■:. 

P 

^Hk                    flSP 

^bH 

ymmamm  Vf 

w 

WM  ^^^m'  umw 

W     :' 

jp  wHMSKHpP 

1 

"■1 

Fig.  39. — Alopecia  (complete). 

No  skin  lesions  are  present  and  no  scars.  The  epitrochlear  glands 
on  both  sides  are  palpable.  The  inguinal  glands  are  slightly  enlarged 
while  the  cervical  glands  are  not  palpable. 

The  left  tonsil  is  greatly  hypertrophied  with  a  denuded  area 
covering  one-fourth  of  the  surface.  The  right  tonsil  is  only  slightly 
hypertrophied.     The  pharynx  is  normal. 

The  superficial  veins  of  both  legs  show  slight  varicosity,  while 
there  is  a  varicocele  of  the  left  side. 
7 


98  CLINICAL  HISTORY 

Pulse  is  60;  systolic  blood-pressure,  130. 

Neurological  examination,  negative. 

Urine,  normal. 

Wassermann,  negative. 

Lumbar  puncture,  refused. 

Treatment. — The  patient  was  placed  on  daily  inunctions  of  4 
grams  of  mercury  with  potassium  iodide  by  mouth  up  to  30  grains 
t.  i.d. 

He  remained  in  the  hospital  until  November  30,  and  as  no 
improvement  was  observed  was  discharged. 

This  patient  left  Hot  Springs  early  in  1915  and  returned  in 
January,  1916,  during  which  time  he  received  no  treatment.  He 
still  showed  a  condition  of  complete  alopecia. 

Nails. — The  affections  of  the  nails  in  syphilis  occur  with  com- 
parative infrequency,  those  of  the  fingers  being  affected  more 
often  than  those  of  the  toes.  Such  affections  usually  occur 
during  the  first  two  years  of  the  disease,  but  may  be  observed 
much  later. 

Onychia. — ^This  condition  is  observed  in  four  different  varieties: 
Onychia  sicca,  or  dry  onychia,  consists  of  a  thinning  and  loss  of 
lustre  of  the  nail.  It  becomes  ragged,  brittle  and  easily  broken. 
The  free  edge  is  thickened  and  of  a  dull  yellow  color.  The  surface 
is  rough  and  presents  fissures  and  depressions.  One  or  several  nails 
may  be  affected.  Hypertrophic  onychia  is  rare,  and  is  marked  by 
thickening  of  the  nail.  Usually  more  than  one  nail  is  affected. 
Partial  detachment  occurs  gradually,  the  process  beginning  at  the 
distal  end  of  the  nail  and  more  or  less  of  the  nail  is  detached  and 
elevated.  The  separated  portion  assumes  a  dirty  yellowish- white 
tint,  with  a  white  line  marking  the  extent  of  the  detachment. 
Complete  detachment  is  merely  a  continuation  of  the  process  de- 
scribed above  until  the  entire  nail  becomes  loosened  and  drops  off, 
leaving  the  nail  bed  bare.  The  latter  soon  becomes  covered  with 
fairly  thick  epidermis.  Only  one  nail  may  be  affected  or  several 
may  be  involved  at  one  time  or  in  succession.  The  nail  is  usually 
replaced  by  a  new  one  if  antisyphilitic  treatment  is  instituted.  A 
fifth  variety  of  luetic  onychia  has  been  described  by  Taylor/  which 
appears  to  be  a  local  necrosis.  Two  to  ten  opaque  whitish  spots 
the  size  of  a  pin-head  are  observed.  These  are  formed  by  depres- 
sions of  the  surface  of  the  nail,  and  soon  reach  the  matrix,  leaving 
minute  sharply  cut  holes.  Sometimes  the  depressions  do  not 
completely  perforate  the  nail  and  the  surface  appears,  as  Taylor 
expresses  it,  like  the  surface  of  a  thimble. 

Paronychia. — This  syphilitic  process  may  begin  in  the  skin 
around  the  nail  and  extend  to  the  matrix  or  it  may  spread  from  the 

1  The  Pathology  and  Treatment  of  Venereal  Diseases,  Philadelphia,  1895,  p.  661. 


SYPHILIS  OF   THE  APPENDAGES  OF   THE  SKIN 


99 


nail.  This  condition  is  observed  both  on  the  toes  and  on  the  fingers, 
and  may  be  confined  to  one  nail,  or,  as  is  usually  the  case,  several 
may  be  affected  at  once  or  successively.  The  course  is  generally 
very  chronic. 


Fig.  40. — Onychia  and  parony 


According  to  Taylor,^  three  varieties  of  paronychia  are  observed: 

Indolent   or   non-ulcerative   paronychia   may    attack   the   entire 

attached  margin  of  the  nail,  the  lunula,  or  only  one  of  the  lateral 

margins.    A  dull  red  papular  rim  about  2  mm.  broad  is  seen  around 


jg^ 

S               mim*-^ 

^^% 

^, 

Fig.  41. — Onychia  and  paronychia. 

the  border  of  the  nail.    The  condition  may  be  acute  or  chronic. 
In  the  chronic  form  the  nail  itself  may  become  involved. 

Ulcerative  paronychia  may  begin  as  a  papule  or  pustule  at  the 
nail  margin  or  as  a  small  ulcer  at  the  lunula.    The  process  gradually 


1  The  Pathology  and  Treatment  of  Venereal  Diseases,  Philadelphia,  1895,  p.  662. 


100  CLINICAL  HISTORY 

extends  and  may  undermine  the  entire  nail,  the  latter  falling  off. 
If  the  condition  is  not  too  severe,  a  new  nail  will  develop. 

Diffuse  paronychia  begins  as  a  hyperemia  and  reddened  condition 
of  the  distal  ends  of  the  digit.  Later  the  red  fades  to  a  coppery 
hue  and  the  part  becomes  swollen  and  club-shaped.  The  nail 
becomes  affected,  being  swollen,  uneven  and  of  a  black  and  green 
color.  While  the  process  usually  is  not  severe  enough  to  cause  the 
loss  of  the  nail,  this  does  sometimes  occur.  If  the  matrix  is  not 
destroyed,  a  new  nail  will  develop. 


MUCOUS  MEMBRANES. 

The  syphilomycodermata  are  among  the  most  important  symptoms 
of  syphilis  and  a  thorough  understanding  of  them  is  most  desirable. 

Macular  Syphilomycoderm. — ^The  erythematous  macular  syphilo- 
mycoderm  occurs  early  in  the  course  of  the  disease,  usually  with  the 
first  cutaneous  lesions,  although  it  may  be  the  first  manifestation 
of  syphilis  following  the  chancre,  ana  often  passes  unnoticed  by 
the  patient. 

This  lesion  is  most  frequently  located  upon  the  fauces,  the 
Schneiderian  membrane  and  genital  organs.  The  tongue,  inner 
surfaces  of  the  cheeks  and  larynx  also  sometimes  are  affected  while 
it  sometimes  occurs  in  the  vagina  and  on  the  cervix.  The  erythema 
may  occur  in  spots  or  patches  of  varying  size  and  shape  similar 
to  the  roseolar  macular  syphiloderm,  or,  as  is  usually  the  case,  it  is 
diffuse,  presenting  a  hyperemia  of  dark  red  color  with  sharply 
defined  outline.  It  may  be  dry  or  it  may  be  covered  by  a  moist 
secretion.  Usually  there  is  no  swelling  but  when  the  Schneiderian 
membrane,  tonsils,  and  vulva  are  affected  there  may  be  considerable 
enlargement.  This  lesion  may  disappear  very  suddenly  but  recur- 
rences are  often  observed.  Usually,  however,  after  a  short  time  the 
affected  area  assumes  a  milky  hue  and  the  superficial  layers  become 
detached,  forming  erosions. 

The  erosive  macular  syphilomycoderm  is  found  most  frequently 
in  the  mouth,  on  the  lips,  tonsils,  tongue  and  cheeks,  on  the  vulva 
and  on  the  glans  and  prepuce.  It  is  also  noted  in  the  larynx  and 
on  the  Schneiderian  membrane.  There  are  usually  multiple  lesions, 
consisting  of  small  rounded  or  oval  spots  of  a  reddish  color,  denuded 
of  the  superficial  layers  and  secreting  a  thin  fluid  in  which  are  found 
many  treponemata.  This  type  of  lesion  is  very  amenable  to  treat- 
ment, disappearing  rapidly  under  the  influence  of  specifics.  It  is 
also  rather  prone  to  recur. 

Papular  Syphilomycoderm. — ^This  variety  of  syphilitic  lesion 
corresponds  quite  closely  in  many  respects  to  its  homologue  of  the 
skin. 


MUCOUS  MEMBRANES  101 

The  erosive  form  of  the  papular  syphilomycoderm  is  usually  an 
early  manifestation,  appearing  during  the  first  year  of  the  disease, 
but  may  be  observed  later.  It  is  found  most  frequently  in  the* 
mouth,  on  the  external  genital  organs  of  the  female  and  around  the 
anus.  The  Schneiderian  membrane  and  the  larynx  are  also  some- 
times affected,  while  this  lesion  has  been  described  as  occurring 
in  the  vagina  and  on  the  cervix  uteri.  It  is  the  most  common  of  all 
the  syphilomycodermata  and  is  the  one  most  frequently  designated 
mucous  patch. 

It  usually  begins  as  a  round  red  spot  on  the  mucous  membrane. 
It  may  be  single  but  more  frequently  is  multiple.  It  is  slightly 
elevated  above  the  surrounding  membrane,  the  surface  is  denuded 
of  epithelium,  as  in  the  erosive  macular  lesion,  and  is  covered  by  a 
moist  secretion  containing  many  treponemata.  This  lesion  varies 
in  size  from  a  millimeter  to  1  or  2  cm.  in  diameter  and  several 
papules  may  become  confluent.  At  first  reddish  in  color  it  may 
deepen  almost  to  a  purple,  or  it  may  become  lighter  in  shade, 
even  assuming  a  grayish  or  whitish  color.  Not  infrequently  the 
centre  of  the  lesion  may  be  of  a  light  color  while  the  periphery 
remains  a  dark  red.  The  shape  depends  somewhat  on  the  location 
but  generally  is  circular  or  nearly  so. 

The  ulcerative  papular  lesion  of  the  mucous  membrane  usually 
follows  the  last-described  lesion  and  generally  is  produced  by 
such  untoward  circumstances  as  uncleanliness,  the  use  of  tobacco, 
the  irritation  of  a  decayed  or  jagged  tooth,  etc.  It  is  essentially  a 
papule  with  an  ulcerating  surface.  The  ulceration  may  be  super- 
ficial or  deep,  the  former  being  little  more  than  an  erosion.  The 
deep  ulcer  presents  a  raised,  sharply  cut  edge  with  an  indurated 
dark  red  or  yellow  base.  Occasionally  the  lesion  is  covered  by  an 
exudation  which  resembles  the  false  membrane  of  diphtheria, 
therefore  the  term  diphtheroid  is  sometimes  used. 

Sometimes,  especially  upon  the  tongue  and  lips,  deep  ulcerating 
cracks  or  fissures  may  develop.  When  upon  the  lips  considerable 
deformity  may  result,  due  to  the  formation  of  crusts  by  the  secretions 
and  hemorrhage  from  the  lesion.  Upon  the  tongue  the  fissures  may 
be  parallel  to  the  long  axis  of  the  organ  or  star-shaped.  Permanent " 
scars  may  be  left  upon  healing.  Multiple  lesions  are  usually  present 
and  they  vary  greatly  in  size  and  shape. 

The  vegetative  or  hypertrophic  papular  syphilomycoderm  is  less 
frequently  observed  than  the  ulcerative  types.  It  is,  however,  a  later 
stage  of  the  erosive  papular  lesion  and  is  practically  only  found 
where  cleanliness  is  not  practised.  The  most  frequent  location  in 
which  this  condition  is  observed  is  around  the  anus  and  vulva,  less 
frequently  it  is  found  in  the  mouth,  especially  on  the  under  surface 
of  the  tongue,  and  occasionally  in  the  larynx.    It  is  also  sometimes 


102  CLINICAL  HISTORY 

observed  on  the  cervix  uteri.  It  appears  as  a  roughened,  warty  mass 
and  when  situated  about  the  anus  or  vulva  usually  involves  the 
surrounding  skin  as  well  as  the  mucous  membrane.  It  varies  in 
size  from  two  or  three  millimeters  to  several  centimeters  and  may  be 
elevated  as  much  as  one  centimeter  or  more  above  the  surrounding 
surface.  When  occurring  on  the  under  surface  of  the  tongue  the 
vegetating  syphilomycoderm  rarely  is  elevated  more  than  1  or  2  mm., 
and  instead  of  the  usual  reddish  color  of  this  lesion  in  other  localities 
a  dull  gray  or  whitish  color  is  observed. 

The  surface  of  this  lesion  may  be  dry  or  ulcerative.  If  the  latter 
condition  is  present,  there  is  usually  a  more  or  less  profuse  secretion 
which  contains  many  treponemata  and  may  have  an  extremely 
foul  odor. 

The  squamous  papular  syphilomycoderm  is  a  comparatively 
rare  condition,  and  consists  of  a  papular  lesion  on  the  mucous 
membrane,  which,  instead  of  becoming  eroded  or  ulcerated,  is  dry, 
smooth  and  shiny,  while  desquamation  of  the  superficial  layers 
of  the  epithelium  usually  occurs.  It  is  generally  found  during  the 
first  two  years  of  the  disease  but  may  appear  much  later  and  is 
most  frequently  noted  in  the  mouth. 

Leukoplakia  is  a  condition  of  the  mucous  membrane  which  consists 
of  a  grayish  or  whitish  discoloration  and  more  or  less  thickening 
and  has  been  described  as  appearing  as  if  the  part  had  been  touched 
with  silver  nitrate.  While  leukoplakia  is  more  frequently  seen  in 
the  mouth,  it  is  found  on  most  of  the  other  mucous  surfaces,  especi- 
ally on  the  vulva  and  penis.  One  striking  feature  of  this  condition 
is  the  frequency  with  which  it  is  followed  by  epitheliomata. 
Leukoplakia  has  been  described  as  the  homologue  of  the  palmar 
and  plantar  syphilodermata.  When  the  condition  is  very  severe  this 
description  is  very  apt.  Erosion  and  ulceration  of  the  patches  of 
leukoplakia  is  a  not  infrequent  occurrence  and  fissures  may  develop 
with  or  without  the  last-mentioned  condition. 

Gummatous  Syphilomycodermata. — The  mucous  membranes  are 
very  prone  to  be  attacked  by  gummatous  formation  and  as  with  the 
gummata  of  the  skin  usually  occur  late  in  the  course  of  the  disease, 
but  may  develop  early.  Gummatous  syphilomycodermata  are 
found  on  all  of  the  mucous  surfaces  and  present  more  or  less  varying 
pictures,  depending  upon  their  location.  Gummata  of  the  mucous 
membranes  of  the  mouth  may  occur  upon  the  tongue,  lips,  cheeks, 
tonsils  or  palate.  They  vary  in  size  from  1  mm.  to  1  or  2  cm.  in 
diameter  and  may  be  single  or  multiple,  circumscribed  or  con- 
fluent. When  situated  on  the  tongue  this  type  of  lesion  is  usually 
found  on  the  dorsum  near  the  tip  or  edges.  Multiple  lesions  are 
generally  observed.  The  mucous  membrane  is  at  first  of  natural 
color  but  soon  becomes  redder  and  smoother,  and  usually  in  a  few 


GENERAL  SYMPTOMS  103 

weeks  the  lesions  soften  and  ulceration  takes  place.  On  the  palate 
the  gumma  is  comparatively  frequent  and  when  present  projects 
as  a  flattened  tumor  above  the  surface.  Gummata  of  the  lips  and 
mucous  membrane  of  the  cheeks  are  exceedingly  rare. 

Gummata  of  the  larynx  is  not  infrequently  observed  but  are 
usually  seen  after  ulceration  takes  place. 

Ulcerating  gummata  are  not  rare  on  the  Schneiderian  membrane. 

Gummata  of  the  mucous  membranes  of  the  female  genital  organs 
are  noted  rather  rarely,  and  more  often  seen  on  the  vulva  than  in  the 
vagina  in  which  latter  location  they  are  exceedingly  rare.  While 
generally  multiple  and  of  small  size  they  may  be  single  and  rather 
large.  Ulceration  usually  is  delayed  but  when  started  develops 
with  great  rapidity. 

Gummatous  lesions  of  the  mucous  membrane  of  the  penis  are 
seen  not  infrequently,  and  are  most  often  observed  from  the  fourth 
to  the  tenth  or  fourteenth  year.  This  type  of  lesion  is  the  so-called 
chancre-red'ux,  and  the  most  common  location  is  at  the  balano- 
preputial  fold  or  at  the  urinary  meatus.  Ulceration,  either  super- 
ficial or  deep,  may  occur.  Gummata  of  these  regions  are 
important,  especially  on  account  of  the  differential  diagnosis  from 
chancre. 

GENERAL  SYMPTOMS. 

Malaise. — Soon  after  the  appearance  of  the  chancre,  but  before  any 
evidence  of  further  invasion  of  the  body  has  occurred,  there  may  be 
a  general  malaise.  The  patient  feels  weak  and  tires  easily.  The 
expression  of  the  face  is  sad  and  there  is  a  tired,  dejected  look  from 
the  eyes.  This  condition  may  also  be  observed  at  nearly  any 
period  during  the  subsequent  course  of  the  disease. 

Anorexia. — The  appetite  of  the  syphilitic  is  usually  more  or  less 
impaired,  especially  during  the  so-called  second  incubation  period 
and  during  the  active  manifestations  of  the  disease.  However, 
during  the  second  incubation  period  bulimia  may  exist  and  may 
be  very  suggestive. 

Temperature. — During  the  course  of  the  chancre  there  is  usually 
no  deviation  of  the  temperature  from  normal.  In  the  phagedenic 
type  of  chancre,  however,  there  may  be  a  rise  of  temperature. 
The  early  adenitis  also  is  rarely  accompanied  by  fever  but  in  mixed 
infections  when  suppuration  takes  place  a  rise  of  temperature  may 
be  observed.  The  so-called  syphilitic  fever  occurs,  as  a  rule,  late 
in  the  second  incubation  period  and  also  as  an  accompaniment 
of  the  cutaneous  lesions.  It  is  not  at  all  constant  but  is  usually 
found  in  weak  and  undernourished  individuals  and  more  frequently 
in  women  than  in  men.  Two  types  of  fever  are  observed:  the 
continous  and  the  remittent.    The  temperature  occurring  before  the 


104  CLINICAL  HISTORY 

cutaneous  manifestations  is  usually  continuous,  rarely  going  above 
38.5°  C.  (101°  ¥-.).  In  rare  cases  the  temperature  may  rise  to 
39.5°  C,  or  even  40.5°  C.  (103°  F.  to  105°  F.)  during  the  second 
incubation  period  and  then  fall  to  39°  C,  (102°  F.),  upon  the  appear- 
ance of  the  syphilodermata,  to  remain  at  that  period  for  some  time. 
The  remittent  fever  of  syphilis,  as  a  rule,  occurs  late  in  the  course 
of  the  disease  but  may  be  observed  early.  It  is  usually  quotidian 
in  type,  generally  beginning  in  the  late  evening  with  chilly  sensa- 
tions, although  distinct  rigors  seldom  if  ever  occur.  These  are 
followed  by  an  elevation  of  temperature  to  39°  C.  to  40.5°  C. 
(102°  F.  to  105°  F.).  Marked  perspiration  following  the  rise  in 
temperature  is  rare  but  a  slight  amount  may  be  noted. 

Pulse. — ^The  pulse  rate  in  syphilis  usually  is  increased  in  pro- 
portion to  the  temperature,  although  in  some  instances  this  is  not 
the  case,  and  with  a  high  temperature  the  pulse  rate  may  be  increased 
only  moderately. 

Respiration. — ^The  respiratory  rhythm  also,  as  a  rule,  is  increased 
in  proportion  to  the  temperature. 

Polydipsia. — Polydipsia  is  quite  frequently  noted  during  syphilitic 
fever,  especially  if  the  temperature  is  high. 

Blood-pressure. — ^The  blood-pressure  in  syphilis  varies  according 
to  the  portions  of  the  body  involved.  For  example,  the  blood- 
vessels are  very  prone  to  be  the  seat  of  pathological  change  which 
will  raise  the  intravascular  pressure.  Syphilitic  nephritis  may 
also  be  the  cause  of  an  increase  in  the  blood-pressure.  On  the 
other  hand,  the  myocarditis  so  frequently  found  in  syphilis  will 
lower  the  pressure.  However,  it  may  be  said  that,  as  a  rule,  the 
the  blood-pressure  of  syphilitics  is  lower  than  normal. 

Blood. — It  cannot  be  said  that  the  blood  in  syphilis  ever  presents 
a  picture  that  is  pathognomonic.  However,  there  are  certain  changes 
which  are  fairly  constant  at  times  during  the  course  of  the  disease. 
The  most  constant  of  these  is  an  anemia  which  may  occur  at  nearly 
any  time,  but  is  more  frequently  observed  during  the  active  eruption. 
This  anemia  is  secondary  in  type,  the  hemoglobin  being  reduced 
more  markedly  than  the  number  of  the  erythrocytes.  It  is  rarely 
very  severe,  the  hemoglobin  seldom  dropping  below  60  to  70  per 
cent.,  and  the  number  of  erythrocytes  very  infrequently  falling 
below  3,500,000  to  4,000,000. 

Andrews^  quotes  the  case  of  Miiller  in  which  the  erythrocytes 
were  reduced  to  720,000  and  the  hemoglobin  to  18  per  cent.,  giving 
a  high  color  index.  Poikilocytes,  normoblasts  and  megaloblasts 
were  present,  thus  with  the  high  color  index  producing  a  picture  of 
pernicious  anemia.    It  would  seem  that  this  condition  must  have 

1  Power  and  Murphy:  System  of  Syphilis,  London,  1908.  i,  p.  123. 


GENERAL  SYMPTOMS  105 

been  due  to  other  causes  than  syphilis  and  possibly  it  was  a  true 
pernicious  anemia  in  a  syphilitic. 

Leukocytes.— The  most  complete  study  of  the  white  blood  cells 
in  syphilis  which  has  been  made  in  recent  years  was  that  of  Hazen^ 
published  in  1913.  In  125  cases  of  syphilis  with  175  differential 
counts  this  author  reached  the  following  conclusions: 

1.  In  normal  persons  the  average  total  count  is  about  7500, 
the  neutrophile  count  55  per  cent.,  and  the  lymphocyte  count 
33  per  cent. 

2.  In  the  untreated  secondary  cases  there  is  a  slight  leukocytosis, 
an  occasional  case  showing  as  many  as  20,000  white  blood  cells. 
The  eosinophil  es  is  higher  at  this  time  than  in  control  cases  or  in 
cases  of  late  lues.  Treatment  causes  a  slight  drop  in  the  total 
count,  with  a  slight  actual  and  marked  relative  increase  in  the 
lymphocytes. 

3.  Under  treatment  a  secondary  case  may  show  a  lymphocytosis 
as  high  as  65  per  cent.,  a  condition  that  may  persist  for  many  months 
or  that  may  tend  to  approach  normal  in  from  three  to  five  months, 
even  though  treatment  is  continued. 

4.  Cases  of  tertiary  syphilis  very  rarely  show  an  increase  in 
leukocytes.  The  differential  count  in  untreated  cases  is  usually 
not  far  from  normal.  Myelocytes  are  very  rarely  found,  even  with 
moderate  anemia.  Treatment  usually,  but  not  invariably,  causes  a 
rise  in  both  the  relative  and  absolute  number  of  lymphocytes, 

5.  The  cases  with  a  large  papular  eruption,  all  in  this  series 
occurring  in  negroes,  show  a  higher  percentage  of  lymphocytes 
than  do  the  other  types  of  secondary  eruption.  The  average  is  42 
per  cent. 

6.  In  cases  of  secondary  syphilis  negroes  show  a  higher  lympho- 
cytosis (35  per  cent.)  than  do  whites  (26  per  cent.) .  In  the  late  cases 
there  is  not  so  marked  a  difference. 

7.  Males  show  a  slightly  greater  increase  in  the  total  count 
than  do  females;  females  show  a  higher  lymphocyte  count  than 
do  males. 

8.  Age  makes  very  little  difference  in  the  count.  The  very  young 
tend  to  have  a  high  neutrophile  and  a  relatively  low  lymphocyte 
count. 

9.  Marked  glandular  enlargement  does  not  mean  a  high  lympho- 
cytosis, in  fact  there  seems  to  be  very  little  relationship  between 
glandular  involvement  and  the  number  of  small  mononuclears  in  the 
circulating  blood. 

10.  All  cases  of  secondary  syphilis  that  did  badly  under  treatment 
showed  before  treatment   was  begun  a  high  neutrophile  and  a 

1  Jour.  Cut.  Dis.,  1913,  xxxi,  p.  618. 


106  CLINICAL  HISTORY 

low  lymphocyte  count;  all  cases  that  showed  a  low  neutrophile  and 
high  lymphocyte  count  did  well. 

11.  Cases  of  late  hereditary  syphilis  do  not  necessarily  show  a 
high  lymphocyte  count. 

12.  Eosinophil  ia  in  case  of  a  skin  eruption  speaks  against 
syphilis. 

Finally,  it  must  be  remembered  that  evidence  of  involvement 
of  the  viscera,  and  the  osseous,  muscular,  and  nervous  systems 
may  or  may  not  be  present  with  outward  manifestations  of  the 
disease.     These  conditions  will  be  discussed  in  Part  II. 


CHAPTER  VL 
CLINICAL  DIAGNOSIS. 

The  importance  of  the  diagnosis  of  syphilis  is  hardly  to  be  over- 
estimated. Not  only  must  the  presence  of  syphilis  be  recognized 
that  its  course  may  be  checked  and  the  individual  restored  to  normal 
for  his  own  sake  as  well  as  for  the  protection  of  others,  but  it  is  also 
of  the  utmost  importance  that  the  absence  of  syphilis  be  determined 
that  the  individual  may  not  be  stamped  with  the  stigma  of  a  disease 
which  might  be  fraught  with  dire  consequences. 

Three  classes  of  patients  present  themselves  for  diagnosis: 
(1)  those  with  symptoms  or  lesions  which  they  themselves  consider 
syphilitic,  (2)  those  with  symptoms  or  lesions  of  which  they  them- 
selves are  doubtful,  and  (3)  those  with  absolutely  no  thought  of 
syphilis  in  their  minds.  The  latter  class  is  probably  the  most 
important  and  in  the  vast  majority  of  cases  they  are  the  ones  which 
most  try  the  acumen  of  the  physician. 

The  first  and  one  of  the  most  important  features  of  the  diagnosis 
is  the  history,  not  only  the  history  of  the  present  illness,  but  the 
family  and  past  history  of  the  individual.  It  is  a  fact,  however, 
that  quite  a  large  percentage  of  syphilitics  will  not  tell  the  truth, 
or  at  least  the  whole  truth,  concerning  their  past,  therefore  too  much 
reliance  is  not  to  be  be  placed  upon  a  negative  history. 

The  next  step  in  the  diagnosis  is  physical  examination.  Not  only 
should  the  lesions  or  symptoms  which  have  brought  the  patient  to 
the  physician  be  considered  but  the  entire  body  should  be  examined, 
including  a  thorough  neurological  examination  and  the  use  of  such 
instruments  as  the  sphigmomanometer,  the  stethoscope,  and  the 
opthalmoscope. 

The  use  of  the  .T-rays  may  be  desirable  in  certain  cases,  and  these 
will  be  suggested  by  the  history  or  physical  examination. 

The  laboratory  procedures  will  also  be  determined  by  the  history 
and  physical  examination  and  should  always  include  a  urinalysis 
and  a  Wassermann  test  upon  the  blood.  The  latter  should  be  per- 
formed in  some  cases,  perhaps  not  so  much  for  the  diagnostic 
value  as  for  a  guide  to  treatment. 

The  author  is  of  the  opinion  that  all  cases  of  proven  syphilis, 
especially  those  with  abnormal  neurological  findings,  should  have 
a  spinal  puncture  performed  to  determine  whether  or  not  the  central 


108  CLINICAL  DIAGNOSIS 

nervous  system  has  been  invaded,  so  that  if  it  has,  specific  treatment 
may  be  directed  toward  it.  Finally,  the  diagnosis  may  have  to  rest 
upon  therapeutic  grounds.  That  is,  if  all  other  means  fail,  the 
improvement  of  certain  symptoms  and  lesions  upon  the  adminis- 
tration of  specific  remedies  will  be  very  strong  presumptive  evidence 
that  the  symptoms  and  lesions  are  due  to  syphilis. 

CHANCRE. 

The  diagnosis  of  chancre  of  all  the  manisfestations  of  syphilis  is 
perhaps  of  the  most  importance.  This  is  true,  because  in  the  vast 
majority  of  cases  if  diagnosed  while  the  chancre  is  the  only  lesion 
present,  the  successful  outcome  of  the  treatment  may  be  assured. 

Genital  Chancre. — The  presumptive  diagnosis  of  genital  chancre 
can  probably  be  made  in  the  majority  of  cases  by  the  history,  if 
this  can  be  obtained,  by  the  general  appearance  and  by  the  indura- 
tion, but  the  author  is  of  the  opinion  that  a  definite  diagnosis  of 
syphilitic  chancre  without  further  clinical  evidence  is  seldom,  if 
ever,  justifiable  without  the  finding  of  the  Treponema  pallidum 
or  a  positive  Wassermann  test. 

The  most  important  condition  to  be  differentiated  from  chancre 
is  chancroid. 

The  following  table  shows  the  main  points  of  differentiation: 

Chancre.  Chanceoid. 

1.  Incubation   three   to    four   weeks,  1.  Short.     Usually  under  five  days, 
rarely  under  ten  days. 

2.  Papule,  erosion  or  ulcer  with  slop-  2.  Pustule  or  ulcer  with  sharply  cut 
ing  edges. 


3.  Usually  single.  3.  Usually  multiple. 

4.  Scanty  serosanguineous  discharge.  4.  Abundant  purulent  discharge. 

5.  Indurated  base.  5.  Soft  or  inflammatory  base. 

6.  Treponema  pallidum.  6.  Bacillus  of  Ducrey. 

7.  Wassermann  positive  or  negative.  7.  Always  negative. 

It  must  be  remembered  that  chancre  and  chancroid  are  very 
frequently  associated  in  the  so-called  mixed  sore  which  will  render 
the  diagnosis  less  certain  owing  to  the  greater  difficulty  of  demon- 
strating the  organisms  of  syphilis.  It  is  the  custom  of  the  author 
with  all  cases  diagnosed  chancroid  by  the  finding  of  the  bacillus 
of  Ducrey  and  the  failure  to  find  the  Treponema  pallidum  to  make 
Wassermann  tests  quite  frequently,  at  least  every  two  or  three  days, 
for  several  weeks,  until  all  danger  of  a  concomitant  syphilitic  infec- 
tion is  past.    . 

Chancre  must  be  differentiated  from  simple  erosion,  and  can 
usually  be  done  by  the  absence  of  induration  and  adenitis  in  the 
latter  condition  as  well  as  by  the  failure  to  find  treponemata. 


CHANCRE  109 

Herpes  may  sometimes  be  mistaken  for  chancre,  but  in  the 
majority  of  cases  the  multiphcity  of  the  lesions,  or  if  single  they 
are  made  up  of  numerous  small  intersecting  segments  of  circles, 
the  presence  of  burning  and  itching,  the  usual  absence  of  induration 
and  adenitis,  and  the  absence  of  treponemata,  will  serve  to  diagnose 
the  condition. 

Occasionally  the  ulcerated  or  papular  lesion  of  scabies  may  be 
mistaken  for  chancre.  As  with  herpes,  there  is  usually  little  or  no 
induration  and  adenitis  and  of  course  the  organism  of  syphilis  is 
never  found. 

Gummata  sometimes  very  closely  resemble  chancre  and  consti- 
tute, at  least  in  most  instances,  the  so-called  chancre  redux.  They 
are  to  be  differentiated  from  true  chancre  by  the  history,  that  is 
with  gummata,  a  history  of  sjqDhilis,  and  with  chancre  a  history  of 
exposure,  and  by  the  typical  adenitis  seen  with  chancre  and  almost 
always  absent  with  gumma.  Treponemata  may  be  found  in  both 
conditions,  although  more  abundantly  in  the  chancre.  The  Wasser- 
mann  test  may  be  positive  or  negative  in  either,  while  the  luetin 
test  is  more  frequently  positive  with  gummata. 

Chancre  of  the  urethra  may  simulate  gonorrhea  but  shows  less 
discharge,  the  nature  of  which  is  serosanguineous  rather  than  puru- 
lent, as  with  gonorrhea.  The  chancre  can  usually  be  palpated  or 
observed  by  the  endoscope  and  treponemata  demonstrated  in 
the  discharge. 

Chancre  of  the  cervix  may  be  mistaken  for  epithelioma.  In  the 
latter  condition  cachexia  is  usually  marked,  even  early,  hemorrhage 
is  frequent,  pain  is  present,  also  the  discharge  is  more  copious  and 
very  offensive.  Treponemata  cannot  be  found  in  epithelioma, 
while  the  typical  histological  picture  of  the  latter  may  be  demon- 
strated by  making  a  section  of  the  lesion. 

Chancre  of  the  rectum  may  resemble  simple  fissure,  but  is  less 
painful  and  is  associated  with  an  adenitis  of  the  inguinal  region, 
which  is  not  observed  with  simple  fissure,  while  treponemata  may 
be  demonstrated. 

Extragenital  chancres  usually  present  more  difficulty  of  diagnosis 
than  genital  chancres.  This  is  due,  partially  at  least,  to  their  com- 
parative rarity  and  to  the  fact  that  often  neither  the  patient  nor 
the  physician  is  suspicious  of  s}T)hilis. 

Labial  chancre  is  not  infrequently  mistaken  for  epithelioma. 
The  latter,  however,  occurs,  as  a  rule,  later  in  life  than  chancres, 
presents  an  irregular  vegetating  surface  with  thickened  edges, 
bleeds  easily,  is  followed  by  adenitis  much  later,  and,  finally,  con- 
tains no  treponemata,  but  does  present  on  section  the  tj^jical 
histological  picture  of  malignant  growth. 

Chancre  of  the  tonsil  may  present  considerable  difficulty  in  diag- 


110  CLINICAL  DIAGNOSIS 

nosis.  It  is  to  be  differentiated  from  cancer,  abscess,  simple  angina, 
diphtheria,  Vincent's  angina,  and  gummata. 

Cancer  usually  appears  later  in  life  than  does  chancre,  bleeds 
easily,  there  is  more  cachexia,  the  adjacent  glands  enlarge  later, 
and  the  histological  picture  of  cancer  is  found  on  section. 

Abscess  of  the  tonsil  is  usually  of  more  sudden  onset,  the  pain  is 
more  severe,  swallowing  and  even  motions  of  the  head  and  neck  are 
more  difficult,  while  chills  and  fever  with  headache,  backache,  and 
general  malise  are  more  frequent  and  severe. 

Simple  angina  is  to  be  differentiated  from  chancre  of  the  tonsil 
by  the  ease  with  which  it  usually  improves  under  treatment  and 
from  the  fact  that  simple  angina  is  generally  bilateral,  while  chancre 
is  most  often  found  on  but  one  tonsil. 

Diphtheria  and  Vincent's  angina  should  always  be  diagnosed  by 
the  finding  of  the  causative  organisms. 

Gumma  of  the  tonsil  may  resemble  chancre,  but  may  be  distin- 
guished from  the  latter  by  the  absence  of  glandular  enlargement. 

Lingual  chancre  may  simulate  epithelioma  and  the  differential 
diagnosis  is  the  same  as  labial  chancre. 

Simple  or  dental  ulcer  may  be  mistaken  for  chancre  of  the  tongue, 
but  the  presence  of  a  broken  tooth  and  the  absence  of  glandular 
enlargements  are  usually  sufficient  to  establish  the  diagnosis. 

Chancre  of  the  tongue  sometimes  resembles  a  tubercular  ulcer; 
however,  tubercular  lesions  are  usually  multiple,  while  chancre  is 
generally  single,  induration  is  present  in  chancre  and  is  not  in  tuber- 
cular ulcer  unless  it  has  been  cauterized,  and  with  tubercular  ulcer 
other  tubercular  lesions  are  usually  seen.  Finally,  in  tubercular 
ulcer  the  tubercle  bacillus  can  usually  be  demonstrated,  either  by 
microscopic  examination  or  by  inoculation  of  a  guinea-pig. 

It  must  be  remembered  in  examining  the  secretion  of  all  oral 
chancres  for  the  Treponema  pallidum  that  the  Treponema  micro- 
dentium  very  closely  resembles  the  organism  of  syphilis  and  must 
be  differentiated  from  it.     (See  page  125.) 

Chancre  of  the  breast  may  be  confounded  with  fissure  of  the  breast, 
carcinoma,  or  gumma.  Fissure  of  the  breast  is  more  painful  than 
chancre,  bleeds  more  easily,  is  less  indurated,  and  is  not  associated 
with  glandular  enlargement. 

Carcinoma  of  the  breast  presents  practically  the  same  points  of 
differential  diagnosis  as  carcinoma  of  the  lip  and  tongue. 

Gumma  of  the  breast  is  not  associated  with  glandular  enlarge- 
ment. 

Treponemata  should  be  found  in  all  untreated  chancres  of  the 
breast,  and  very  sparingly  if  at  all  in  gummata. 

Chancre  of  the  eyelid  should  present  little  or  no  difficulty  of  recog- 
nition, though  it  may  be  mistaken  for  a  tubercular  lesion  or  a 


LYMPHATIC  GLANDS  111 

carcinoma.    The  differential  diagnosis  is  the  same  as  that  described 
under  Lingual  Chancre. 

Digital  chancre  more  frequently  remains  undiagnosed  until 
other  manifestations  of  syphilis  appear  than  chancre  of  any  other 
locality.  This  is  probably  due  to  the  fact  that  induration  can 
rarely  be  demonstrated  in  chancre  of  the  finger,  and  that  it  is  very 
frequently  complicated  by  suppuration.  The  latter  condition 
renders  the  diagnosis  most  difficult  owing  to  the  uncertainty  of 
demonstrating  the  treponema.  In  some  cases  the  diagnosis  may 
have  to  be  deferred  until  the  Wassermann  becomes  positive. 

LYMPHATIC   GLANDS. 

The  diagnosis  of  the  adenitis  occurring  soon  after  the  chancre 
and  in  the  glands  adjacent  to  this  lesion  will  largely  depend  upon 
the  diagnosis  of  the  chancre.  However,  the  nature  of  this  adenitis 
may  assist  in  the  diagnosis  of  the  latter.  In  chancre  more  than  one 
gland  is  usually  enlarged,  they  are  hard,  firm,  and  painless,  and 
present  a  marked  contrast  to  the  single  large  soft,  boggy,  and  painful 
gland  of  chancroid.  With  chancre,  also,  bilateral  enlargement  is 
the  rule,  while  with  chancroid  the  enlargement  is  usually  on  one 
side  only.     Treponemata  may  also  be  found. 

The  later  enlargement  of  the  lymph  glands,  especially  the  epi- 
trochlears,  occipital  and  posterior  cervical,  are  of  more  or  less  diag- 
nostic importance.  Friedlander^  has  shown  that  unilateral  enlarge- 
ment of  the  epitrochlears  is  found  in  86  per  cent,  of  syphilitics, 
while  such  enlargement  is  present  in  only  42.5  per  cent,  of  non- 
sj^hilitics;  the  occipitals  show  82  per  cent,  unilateral  enlargement 
in  syphilitics  and  52  per  cent,  in  non-syphilitics ;  and  the  posterior 
cervicals  84  per  cent,  in  syphilitics  and  60  per  cent,  in  non-syphilitics. 

Bilateral  enlargement  is  more  striking,  the  epitrochlears  being 
enlarged  in  77  per  cent,  of  syphilitics  and  in  only  27.5  per  cent, 
of  non-syphilitics.  The  occipital  glands  also  show  enlargement  in 
77  per  cent,  of  syphilitics  and  in  45  per  cent,  of  non-syphilitics, 
while  the  posterior  cervicals  show  80  per  cent,  bilateral  enlarge- 
ment in  syphilitics  and  47  per  cent,  in  non-syphilitics. 

It  is  therefore  seen  that  bilateral  enlargement,  especially  of  the 
epitrochlears,  is  to  be  looked  upon  with  marked  suspicion. 

The  enlarged  epitrochlears  lie  in  the  groove  above  the  epicondylar 
ridge  of  the  humerus,  behind  the  inner  margin  of  the  biceps  and 
usually  about  one  inch  above  the  condyle,  although  they  may  be 
considerably  higher.  The  elbow  should  be  flexed  for  palpation, 
the  most  important  condition  from  which  syphilitic  lymph  glands 


1  Jour.  Cut.  Dis.,  1912,  xxx,  p.  14. 


112  CLINICAL  DIAGNOSIS 

are  to  be  distinguished  in  tubercular  enlargements.  This  may 
usually  be  accomplished  by  the  history,  by  the  finding  of  other 
clinical  evidence  of  one  or  the  other  of  the  two  diseases,  and  by  the 
tuberculin  and  Wassermann  tests: 

CUTANEOUS  LESIONS. 

The  skin  lesions  of  syphilis  may  simulate  almost  any  form  of 
cutaneous  disease.  There  are,  however,  in  the  majority  of  cases 
certain  distinguishing  features  which  enable  the  clinician  to  make 
a  correct  diagnosis.  The  chief  of  these  characteristics  of  the  syphilo- 
dermata  are  the  following: 

1.  Their  dark  red,  ham,  or  coppery  color. 

2.  Their  usual  freedom  from  pain  or  pruritus. 

3.  Their  usual  development  with  little  or  no  fever. 

4.  Their  comparatively  slow  development. 

5.  Their  tendency  to  polymorphism. 

6.  Their  frequent  location  on  flexor  surfaces. 

7.  Their  usual  firm  consistency. 

8.  Their  tendency  to  circular  arrangement. 

9.  The  frequent  development  of  papules. 

10.  The  usual  circular  formation  and  small  size  of  the  lesions 
developing  early  in  the  course  of  the  disease. 

11.  The  usual  white  color  and  non-adherence  of  the  scales. 

12.  The  greenish  or  black  color,,  the  irregularity,  thickness  and 
adherence  of  the  crusts. 

13.  The  tendency  of  the  ulcers  to  kidney  or  horseshoe  shape. 
Nevertheless  even  with  these  characteristics  in  mind  in  some  cases 

the  diagnosis  on  clinical  evidence  alone  cannot  be  made  and  recourse 
to  laboratory  procedures  or  even  therapeutic  tests  must  be  had. 

The  roseolar  macular  syphiloderm  usually  presents  little  or  no 
difficulty  in  diagnosis.  The  chancre  is  generally  still  present  when 
this  type  of  lesion  is  seen  and  other  evidences  of  syphilis,  such  as  sore 
throat,  lesions  of  the  mouth,  falling  of  the  hair,  adenitis,  etc.,  are 
nearly  always  to  be  found.  The  principal  conditions  from  which  this 
sjT^hiloderm  must  be  differentiated  are  rubeola,  rubella,  tinea  versi- 
color, and  the  rashes  sometimes  following  the  use  of  such  drugs  as 
belladonna,  cubebs,  copaiba,  opium,  sulphonal,  etc. 

Measles  is  to  be  differentiated  by  the  catarrhal  symptoms  and 
fever,  the  eruption,  which  is  generally  crescentic  and  blotchy  in 
character,  and  begins,  as  a  rule,  on  the  face  and  neck.  It  must  be 
remembered,  however,  that  in  syphilis  the  fever  may  at  times  be  high. 

In  German  measles  the  eruption  shows  no  tendency  to  pigmenta- 
tion, is  of  short  duration,  and  is  accompanied  by  slight  catarrhal 
symptoms. 


CUTANEOUS  LESIONS  113 

Tinea  versicolor  can  usually  be  diagnosed  by  the  peculiar  distri- 
bution and  the  finding  of  the  Microsporon  furfur. 

Of  the  drug  rashes  that  following  the  ingestion  of  copaiba  is  prob- 
ably of  the  most  importance,  owing  to  the  frequency  of  the  adminis- 
tration of  this  drug  in  gonorrhea.  The  drug  rashes  are,  as  a  rule,  of 
a  much  more  vivid  "red  or  scarlet  color  than  the  roseolar  syphiloderm, 
are  of  short  duration  and  almost  always  accompanied  by  more  or 
less  pruritus. 

The  annular  macular  syphiloderm,  which  is  a  rare  condition,  should 
be  diagnosed  by  the  history,  the  character  of  the  eruption,  and  some- 
times the  presence  of  concomitant  lesions  of  syphilis. 

The  pigmentary  syphiloderm  in  the  superpigmentation  stage, 
according  to  Taylor,^  is  to  be  differentiated  from  chloasma,  and  this 
may  usually  be  accomplished  by  the  history.  Later  when  the  white 
spots  are  present  vitiligo  may  be  simulated.  The  location,  usually 
on  the  sides  of  the  neck,  of  the  syphiloderm  and  the  absence  of  a 
distinct  brown,  narrow  margin  which  is  characteristic  of  vitiligo 
should  serve  as  distinguishing  features. 

Tinea  versicolor  may  be  differentiated  by  the  location,  which  is 
rare  on  the  sides  of  the  neck  alone,  the  darker  color,  the  slightly 
elevated,  scaly  lesions,  the  itching  and  the  finding  of  the  causative 
organism. 

The  diagnosis  of  the  miliary  papular  syphiloderm  is  usually  quite 
easily  made  by  the  history  (perhaps  the  presence  of  the  chancre) 
by  the  color,  distribution,  and  grouping  of  the  eruption  and  by  other 
evidences  of  syphilis.  Scabies  may  be  mistaken  for  this  lesion,  but 
should  not  be  so  on  account  of  the  itching  of  scabies,  the  excoria- 
tions caused  by  scratching,  and  the  finding  of  the  ascarus  scabiei. 

Keratosis  pilaris  may  simulate  the  miliary  papular  syphiloderm 
but  may  be  differentiated  by  the  fact  that  it  is  most  marked  on  the 
thighs,  often  limited  to  these  regions,  is  acccompanied  by  pruritus, 
and  shows  no  tendency  to  group  formations. 

The  extreme  pruritus  of  lichen  planus,  its  usual  limitation  to  the 
legs  and  forearms,  its  slow  progression  and  its  tendency  to  conflu- 
ence should  serve  to  distinguish  it  from  the  miliary  papular  lesion 
of  syphilis. 

The  early  lesions  of  psoriasis  may  appear  like  this  syphiloderm, 
but  are  not  follicular,  are  more  pronounced  on  the  extensor  surfaces 
of  the  arms  and  legs,  do  not  form  groups,  and  are  always  scaly  and 
never  pustular. 

Papular  eczema  should  be  differentiated  by  the  pruritus,  the  ten- 
dency to  confluence,  the  bright  red  color,  the  usual  limited  distribu- 
tion and  the  frequent  vesicular  formation. 

1  The  Pathology  and  Treatment  of  Venereal  Diseases,  Philadelphia,  1895,  p.  641. 


114  CLINICAL  DIAGNOSIS 

Pityriasis  rubra  -pilaris  is  sometimes  diagnosed  as  syphilis,  but 
this  error  should  not  be  made  when  the  tendency  of  the  lesions  of 
this  disease  to  confluence,  scaliness,  and  lack  of  pustulation  is 
considered. 

The  miliary  papular  syphiloderm  may  simulate  acne,  especially 
when  it  occurs  on  the  forehead,  the  so-called  corona  veneris.  The 
dark  color  and  flat  surface  of  the  syphilitic  lesion  should  distinguish 
it  from  the  conical  acne  pimple. 

Lichen  scrojulosus,  while  a  very  rare  disease,  may  mimic  the 
miliary  papular  syphiloderm  very  strikingly.  The  lesions  are, 
however,  of  a  lighter  color,  are  usually  limited  to  the  trunk,  are  very 
chronic,  and  occur  almost  exclusively  in  childhood  and  nearly  always 
other  evidence  of  scrofulous  diathesis  may  be  found. 

The  lenticulor  or  flat  pajmlar  syphiloderm,  as  it  most  frequently 
appears,  should  be  easy  of  diagnosis.  The  color,  the  distribution, 
the  symmetrical  development,  and  the  usual  absence  of  subjective 
symptoms  are  characteristic,  while  other  manifestations  of  syphilis, 
such  as  adenitis,  syphilomycodermata  and  alopecia  are  usually  present. 

Some  of  the  rarer  varieties  of  this  lesion,  however,  may  present 
more  difficulty. 

Thus,  the  annular  or  circinate  syphiloderm  may  be  mistaken  for 
erythema  multiforme,  which,  however,  is  of  more  sudden  onset,  does 
not  show  the  whitish  appearance  of  the  syphilitic  lesion,  is  most 
frequently  found  on  the  hands  and  forearms,  and  is  accompanied 
by  more  or  less  pruritus. 

This  lesion  may  also  be  mistaken  for  psoriasis,  but  the  scaling 
in  the  latter  disease  is  more  severe,  it  is  seldom  seen  on  the  face  and 
never  when  not  found  elsewhere,  while  slight  bleeding  occurs  upon 
the  removal  of  a  scale,  which  does  not  occur  in  syphilis. 

Tinea  circinata  should  present  no  difficulty  of  differentiation,  as 
it  is  of  slower  development  than  the  annular  syphiloderm,  the  edge 
is  less  indurated  and  more  inflammatory,  while  the  causative  organ- 
ism can  usually  be  demonstrated. 

The  papulosquamous  syphiloderm,  owing  to  its  marked  resemblance 
to  psoriasis,  is  not  infrequently  mistaken  for  that  disease  and  is 
sometimes  erroniously  designated  syphilitic  psoriasis.  The  following 
table  shows  the  main  differential  points : 

Papulosquamous  Syphiloderm.  Psoriasis. 

1.  Location,  may  be  on  face,  on  flexor  1.  Rarely  on  face  or  palms  and  soles, 
surfaces,  perhaps  on  palms  and  soles.  More   on   extensor   surfaces. 

2.  Scaliness     slight     or     moderately  2.  Scaliness  very  marked, 
marked. 

3.  Dull    ham    or    coppery    color.  3.  Bright   or   dark  inflammatory  red 

color. 

4.  Scales  dirty  gray  or  brownish  gray.  4.  Scales  shining,  white  and  lustrous. 

5.  Pruritus   slight   or   absent,    except  5.  Pruritus  rather  frequent, 
in  negro. 

6.  History  of  chancre  and  concomi-  6.  Not  present, 
tant  symptoms  of  syphilis. 


CUTANEOUS  LESIONS  115 

When  the  papulosquamous  syphiloderm  is  found  on  the  palms 
and  soles  the  terms  palmar  and  plantar  syphiloderm  are  applied. 
When  the  lesion  is  limited  to  the  palms  it  frequently  presents 
considerable  difficulty  of  diagnosis.  It  may  somewhat  resemble 
psoriasis,  but  this  disease  rarely  or  never  is  confined  to  these  regions. 

Squamous  eczema  should  be  differentiated  by  the  greater  inflam- 
matory condition  Math  more  or  less  heat  and  itching,  the  more  fre- 
quent location  on  the  fingers  or  finger  ends,  the  presence  or  history 
of  discharge  or  moisture  and  the  absence  of  a  tendency  to  annular 
formation.  The  greatest  difficulty  may  be  encountered  in  distin- 
guishing the  palmar  syphiloderm  from  dermatitis  seborrhoica,  which 
however,  is  rare  in  this  region.  Further,  the  latter  disease  shows 
less  tendency  to  form  serpiginous  or  annular  lesions  and  does  not 
show  the  usual  infiltration  of  the  syphiloderm. 

The  moist  papidar  syphiloderm,  the  lenticular  papular  lesion  which 
instead  of  desquamating,  presents  a  more  or  less  moist  appearance, 
is  usually  easy  of  diagnosis.  The  history,  the  location  on  areas 
which  are  kept  moist  with  perspiration,  and  the  usual  accompani- 
ment of  other  syphilitic  manifestations,  in  the  majority  of  cases 
will  enable  the  clinician  to  reach  a  correct  diagnosis. 

Veruca  acuminata  sometimes  quite  closely  resembles  this  lesion, 
but  the  syphiloderm  usually  is  as  broad  at  its  base  as  at  its  summit, 
while  the  acuminate  lesion  is  pedunculated.  This  pedunculated 
condition  may  be  destroyed  by  pressure  and  in  the  absence  of  his- 
tory and  other  manifestations  of  syphilis  the  diagnosis  must  rest 
on  laboratory  procedures. 

The  vesicular  syphiloderm  undoubtedly  is  of  rare  occurrence, 
however  its  rarity  should  make  its  diagnosis  more  important. 
The  appearance  of  small  acuminated,  translucent,  tense,  vesicles 
on  the  back  or  flanks  should  be  looked  upon  with  suspicion.  The 
history  of  chancre,  the  presence  of  other  syphilitic  manifestations 
or  positive  laboratory  evidence  should  make  the  diagnosis  certain. 

The  diagnosis  of  the  bullous  syphiloderm,  which  is  also  a  most 
rare  lesion  in  acquired  s^'philis,  will  rest  upon  practically  the  same 
points  as  the  vesicular  lesion. 

The  pustular  syphilodermata  usually  present  such  characteristic 
appearances  that  an  error  in  diagnosis  should  not  be  made. 

The  acuminate  type  of  this  lesion,  however,  often  quite  markedly 
mimics  acne  or  variola. 

In  acne  there  is  never  any  fever,  it  is  usually  seen  about  the  age 
of  puberty  and  is  confined  to  certain  regions.  It  has  an  inflamed, 
non-indurated  base  and  the  suppuration  extends  deeper  than  in 
the  syphilitic  lesion.  Furthermore,  this  type  of  syphiloderm  usually 
is  accompanied  by  other  manifestations  of  syphilis. 

The  resemblance  of  the  acuminate  pustular  syphiloderm  to  variola 


116  CLINICAL  DIAGNOSIS 

is  sometimes  so  striking  as  to  deceive  even  the  most  skilled.  Not 
only  in  the  occasional  development  of  the  lesions  through  papules, 
vesicles,  and  pustules,  but  in  the  occasional  presence  of  high  fever 
and  more  or  less  umbilication  is  the  similarity  seen.  In  the  majority 
of  cases  of  syphilis,  however,  the  chancre  or  other  luetic  manifesta- 
tions are  present  and  the  development  is  slower.  The  distribution 
of  the  syphilitic  lesion  is,  as  a  rule,  general,  while  the  lesions  of 
smallpox  are  usually  more  marked  on  the  face,  backs  of  the  hands 
and  on  the  wrists.  The  lesion  of  syphilis  ordinarily  has  a  firm 
papular  base,  while  the  variola  lesion  is  all  pustule.  Further,  aside 
from  the  fever,  other  systemic  symptoms  of  syphilis  are  slight, 
while  in  smallpox  they  may  be  severe. 

The  small  flat,  pustular  syphiloderm  must  be  differentiated  from 
pustular  eczema,  especially  when  the  lesions  are  on  the  scalp  or  beard 
and  from  impetigo.  The  syphilitic  lesion  differs  from  the  eczematous 
lesion  in  the  underlying  ulceration,  which  is  not  seen  in  eczema,  and 
in  the  absence  of  pruritus  with  which  eczema  is  usually  associated. 

Impetigo,  as  a  rule,  occurs  on  the  face  and  hands,  runs  a  mild, 
short  course,  is  not  accompanied  by  ulceration,  and  is  more  super- 
ficial than  the  syphiloderm. 

The  only  condition  that  may  be  mistaken  for  the  large  flat,  pus- 
tular syphiloderm  is  ecthyma.  The  syphilitic  lesions  are  generally 
more  numerous  and  are  accompanied  by  ulceration,  while  the  lesions 
of  ecthyma  are  more  painful,  are  not  surrounded  by  the  coppery 
red  border,  and  show  less  tendency  to  crust  formation. 

The  rupial  syphiloderm  is  so  characteristic  that  its  diagnosis 
should  present  no  difficulty.- 

It  is  also  sometimes  necessary  to  differentiate  the  pustular  syph- 
ilodermata  from  the  eruption  caused  by  the  administration  of 
iodin.  As  a  rule  this  can  be  accomplished  without  much  difficulty 
by  the  quicker  onset  of  the  iodin  eruption,  the  brighter  red  color 
and  the  softer  base.  The  withdrawal  of  the  iodin  will  in  the  vast 
majority  of  cases  clear  up  the  diagnosis,  as  an  iodin  eruption  gen- 
erally disappears  when  the  administration  of  the  drug  is  stopped. 

The  diagnosis  of  the  nodular  syphiloderm  is  sometimes  attended 
with  considerable  difficulty.  If,  however,  the  history,  the  color, 
the  tendency  to  form  serpiginous  or  circinate  lesions,  the  usual 
ulceration  and  the  pigmentation  are  considered,  errors  should  be 
rare. 

The  nodular  syphiloderm  may  be  mistaken  for  epithelioma,  but 
this  condition  usually  presents  a  single  lesion,  occurs,  as  a  rule,  later 
in  life  than  syphilitic  lesions,  has  an  infiltrated,  everted  border, 
is  slower  of  progress  and  is  accompanied  by  glandular  enlargements 
and  more  or  less  cachexia.  A  section  of  the  growth,  however,  will 
at  once  settle  the  diagnosis. 


CUTANEOUS  LESIONS  117 

Acne  rosacea  may  resemble  this  syphiloderm,  but  in  the  former 
disease  the  nodules  are  uneven,  usually  vividly  red,  and  situated  on 
a  reddened,  hypertrophied  skin.  There  is  no  tendency  to  form 
serpiginous  or  circinate  lesions,  no  ulceration  occurs  and  dilated 
capillaries  are  generally  present. 

Leprosy  has  not  infrequently  been  mistaken  for  the  tubercular 
syphiloderm  and  vice  versa.  In  leprosy  there  is  usually  a  history 
of  attacks  of  fever,  while  the  lesions  are  generally  softer,  larger,  and 
are  found  most  frequently  on  the  face,  ears,  back  of  the  hands  and 
forearms,  and  areas  of  anesthesia  among  or  around  the  lesions  are 
noted.  The  syphilitic  lesions  are,  as  a  rule,  accompanied  by  a 
history  of  chancre  or  other  syphilitic  manifestations. 

The  gummatous  syphiloderm  may  present  some  difficulty  of  diag- 
nosis, especially  in  the  early  stages  of  its  development,  at  which 
time  it  may  be  mistaken  for  tumors  of  various  kinds,  such  as  fibroid, 
lipoma  and  sarcoma.  Later,  when  softening  takes  place,  a  resem- 
blance to  abscess,  or  suppurating  gland  may  be  seen.  In  the  ulcerat- 
ing stage  the  gummatous  syphiloderm  must  be  differentiated  from 
chancre,  chancroid,  epithelioma,  lupus  and  varicose  ulcer.  The 
history  in  cases  of  gummatous  syphiloderm  may  be  of  no  value,  as 
quite  frequently  this  lesion  develops  many  years  after  infection 
and  the  original  disease  is  forgotten. 

Fibroid  is  usually  more  or  less  pedunculated  and  the  skin  over  it 
is  normal  in  color,  while  gummata  are  sessile  and  are  covered  by  a 
dull  reddish  skin. 

Lipoma  is  more  flattened,  less  globular,  of  softer  consistency  and 
is  less  compressible  than  gumma. 

Sarcomata  are,  as  a  rule,  more  generally  distributed  than  gummata 
and  have  a  predilection  for  the  trunk.  The  skin  over  sarcomata 
is  bluish  or  purplish  in  color  while  the  skin  over  gummata  is  of  a 
dull  red. 

With  any  of  the  above  tumor  formations,  however,  it  may  be 
necessary  to  resort  to  section  of  the  growth  and  microscopic 
examination. 

A  softening  gumma  may  be  mistaken  for  an  abscess  or  suppurat- 
ing gland,  as  such  symptoms  as  redness,  tenderness  and  swelling 
with  even  fluctuation  may  be  present.  There  is,  however,  scarcely 
ever  any  fever  with  gumma,  or  at  most  a  degree  or  so,  and  the 
leukocytes  are,  as  a  rule,  normal  in  number  while  in  abscess  and 
suppurating  glands  fever  and  leukocytosis  are  usually  present. 

Further,  an  incised  gum.ma  will  exude  only  a  small  amount  of 
seropurulent  fluid,  while  the  fluctuation  will  persist. 

The  differential  diagnosis  of  gumma  and  chancre  has  been  given 
above.  (See  page  109.)  Chancroid  is  to  be  distinguished  from  ulcer- 
ating gumma  by  the  history,  the  abundant  purulent  discharge, 
the  adenitis  and  the  finding  of  the  bacillus  of  Ducrey. 


118 


CLINICAL  DIAGNOSIS 


Epithelioma  may  present  some  difficulty  of  differentiation,  but 
if  the  characteristics  of  epithehoma  as  mentioned  under  the  diag- 
nosis of  the  nodular  syphiloderm  be  remembered,  an  error  should 
not  be  made. 

Lupus,  while  resembling  the  ulcerating  gummatous  syphiloderm, 
presents  a  thin,  irregular,  detached,  undermined  and  non-infiltrated 
border,  an  irregular  base,  which  may  not  be  depressed,  and  is 
surrounded  by  a  rose-red  or  bluish  areola. 

Not  infrequently  errors  in  the  differential  diagnosis  of  the  ulcerat- 
ing gummatous  syphiloderm  and  varicose  ulcers  are  made.  The 
following  table  gives  the  main  characteristics  of  each,  which  will 
be  seen  are  quite  different: 


Gummatous  Ulcer. 

1.  Usually  on  upper  part  of  leg,  may 
be  lower  (see  Fig.  37). 

2.  Often  multiple. 

3.  Circular   or  polycyclic   in   outline. 

4.  Edges    sharply    cut,    deep,    some- 
times undermined. 

5.  Base  graduating  or  sloughing. 

6.  Slight    areola,    perhaps    scars    of 
other  ulcers   on   surrounding   skin. 

7.  Other    evidences    of    syphilis,    as 
scars  in  other  locations. 

8.  Varicose  veins  usually  not  present. 

9.  Wassermann  and  luetin  tests  may 
be  positive.     (See  Chapter  VII.) 


Varicose  Ulcer. 

1.  Usually  on  lower  part  of  leg. 

2.  Usually  single. 

3.  Irregular  in  outline. 

4.  Edges,  rounded,  never  undermined. 

5.  Ease     red,     or     gray,     sometimes 
diphtheroid. 

6.  Surrounding  skin  pigmented,  thick- 
ened and  often  eczematous. 

7.  None. 

8.  Varicose   veins   always   present. 

9.  Wassermann  and  luetin  tests  never 
positive. 


Finally,  in  making  a  diagnosis  of  the  skin  manifestations  of  syphilis, 
it  must  be  remembered  that  nearly  any  of  the  skin  diseases  which 
simulate  the  syphilodermata  may  occur  with  the  latter  or  in  indi- 
viduals suffering  with  syphilis  but  without  syphilitic  skin  lesions. 
In  such  cases  the  diagnosis  may  be  extremely  difficult.  If,  however, 
the  history  or  the  laboratory  procedures  pointed  to  syphilis,  specific 
therapy  would  be  justified,  and  the  healing  of  the  lesions  would  be 
very  strong  presumptive  evidence  of  their  syphilitic  nature. 


SYPHILIS    OF    THE    APPENDAGES    OF    THE    SKIN. 

Hair. — As  a  rule  the  diagnosis  of  syphilitic  alopecia  is  attended 
with  no  great  difficulty,  owing  to  the  usual  presence  of  other  mani- 
festations of  syphilis.  In  certain  cases,  however,  as  in  the  author's 
case  of  complete  alopecia  (see  Fig.  39),  the  absence  of  hair  may  be 
the  only  symptom  present.  In  this  case  there  was  a  definite  history 
of  chancre,  followed  by  a  cutaneous  eruption,  which  disappeared 
under  treatment,  the  hair  beginning  to  fall  within  two  weeks  after 
the  appearance  of  the  chancre. 


SYPHILIS  OF   THE  APPENDAGES  OF   THE  SKIN         119 

Syphilitic  alopecia  must  be  differentiated  from  senile  alopecia, 
alopecia  areata  and  premature  alopecia.  The  diagnosis  of  the 
alopecia  due  to  the  presence  on  the  hairy  regions  of  the  various 
syphilodermata,  will  depend  upon  the  diagnosis  of  those  lesions, 
which  has  been  discussed  above. 

Senile  alopecia  differs  from  that  due  to  syphilis  in  the  date  of  its 
appearance,  by  its  location  and  by  its  permanent  character.  The 
falling  of  the  hair  in  senile  alopecia  begins  in  the  region  of  the  temples 
and  on  the  posterior  part  of  vertex  and  from  these  locations  spreads 
backward  and  forward  Syphilitic  alopecia,  on  the  other  hand, 
consists  of  patches  of  baldness  scattered  over  the  scalp. 

Alopecia  areata  is  distinguished  from  syphilitic  alopecia  in  that 
the  spots  are  rounded,  are  absolutely  denuded  of  hair,  and  the  skin 
is  glossy,  white  and  atrophic,  while  in  alopecia  of  syphilitic  origin 
the  spots  are  irregular  in  shape,  are  not,  as  a  rule,  completely 
denuded  of  hair  and  the  skin  is  normal. 

In  premature  alopecia  the  loss  of  hair  corresponds  in  location  to 
that  observed  in  senile  alopecia,  is  gradual  and  permanent,  so  little 
or  no  difficulty  should  be  encountered  in  differentiating  it  from 
syphilitic  alopecia. 

Nails. — Onychia  and  'paronychia  due  to  syphilis  present  in  the 
majority  of  cases  little  or  no  difficulty  of  diagnosis.  They  are 
usually  accompanied  by  other  syphilitic  lesions  or  the  history  of 
such  lesions  may  be  obtained. 

Certain  cases  of  eczema  and  psoriasis  may  present  lesions  resem- 
bling syphilitic  onychia,  and  if  the  history  does  not  clear  the  diag- 
nosis it  may  be  necessary  to  resort  to  laboratory  procedures. 

Paronychia  may  be  mistaken  for  chancre  of  the  finger,  but  in 
chancre  there  will  be  found  enlarged  epitrochlear  and  axillary 
glands. 

Mucous  Membranes. — The  diagnosis  of  the  syphilomycodermata 
when  the  history  is  negative  and  other  lesions  of  syphilis  are  absent 
may  become  most  difficult  and  recourse  to  laboratory  procedures 
must  be  had. 

The  erythematous  macular  lesion  of  the  mucous  membrane  of  the 
mouth  and  throat  usually  occurs  very  early  in  the  course  of  the 
disease,  and  when  it  is  the  only  lesion  present  and  no  history  of 
chancre  is  given  ma,y  readily  be  mistaken  for  a  simple  catarrhal 
angina,  and  diagnosis  without  the  aid  of  the  laboratory  be  impossible. 

The  erosive  macular  syphilomycoderm  may  be  mistaken  for  simple 
erosion  of  the  mucous  membrane,  and  the  diagnosis  of  this  lesion  as 
well  as  the  foregoing  in  the  absence  of  history  of  chancre  or  other 
syphilitic  lesions  may  have  to  rest  on  laboratory  procedures. 
Treponema  pallida  are  usuall}^  abundant  but  must  be  differen- 
tiated from  the  Treponema  microdentium. 


120  CLINICAL  DIAGNOSIS 

The  erosive  papular  syphilomycoderm  must  be  differentiated  from 
simple  erosions  and  when  occurring  in  the  mouth  from  "aphthous 
sores,"  from  herpes  of  the  mouth  and  from  mercurial  ulceration. 

"  Aphthous  sores"  are  usually  more  acute  and  more  sensitive  than 
the  syphilitic  lesions  and  are,  as  a  rule,  associated  with  attacks  of 
indigestion. 

In  herpes  of  the  mouth  the  individual  lesions  are,  usually,  smaller 
than  syphilitic  lesions  and  more  frequently  occur  in  groups. 

The  differentiation  of  mercurial  ulcers  from  the  ulcerative  papular 
syphilomycoderm  may  be  most  difficult.  However,  the  mercurial 
lesion  rarely  is  found  on  the  tongue  or  fauces  which  are  frequent 
sites  of  the  syphilitic  lesion.  The  mercurial  ulcer  is  found  very 
often  on  the  cheeks  or  gum  behind  the  last  molar  tooth  and  on  the 
gum  around  the  upper  or  lower  central  incisors.  These  lesions  are 
also  more  sensitive  than  the  syphilitic  lesions,  and  are  usually 
accompanied  by  other  signs  of  salivation. 

Of  course  the  finding  of  the  Treponema  pallidum  will  differen- 
tiate the  syphilomycoderm  from  all  similar  lesions,  but  if  the  patient 
has  been  under  mercurial  treatment  the  organisms  in  all  probability 
will  not  be  found.  In  such  a  case  it  will  be  necessary  to  discontinue 
the  mercury,  when  if  the  condition  be  due  to  the  drug,  the  lesions 
will  promptly  heal  and  if  they  are  syphilitic,  they  will  not  improve. 

The  ulcerating  papular  syphilomycoderm  is,  as  a  rule,  a  further 
development  of  the  erosive  lesion  and  the  diagnosis  will  depend 
upon  the  same  factors.  Sometimes  an  exudation  is  seen  on  this 
type  of  lesion  which  markedly  resembles  the  false  membrane  of 
diphtheria.  The  differential  diagnosis  will  depend  upon  the  more 
frequent  and  higher  fever  in  diphtheria  and  the  finding  of  the 
causative  organism  of  diphtheria  or  syphilis. 

The  vegetating  or  hypertrophic  lesion  of  the  mucous  membrane 
presents  the  same  diagnostic  features  as  its  homologue  of  the  skin. 

Leukoplakia  is  such  a  characteristic  lesion  that  it  could  scarcely 
be  mistaken  for  any  other  condition.  Psoriasis  of  the  mucous  mem- 
branes might  possibly  be  confused  with  leukoplakia,  but  the  history, 
the  presence  of  other  syphilitic  manifestations  and  positive  labora- 
tory evidence  would  clear  up  the  diagnosis. 

The  gummatous  syphilomycoderm  may  present  similar  difficulties 
of  diagnosis  as  its  homologue  of  the  skin.  Thus  in  its  early  stage 
gumma  of  the  mucous  membrane  may  be  mistaken  for  lipoma, 
fibroid,  or  sarcoma,  while  the  ulcerating  gumma  of  the  mucous 
membrane  must  be  differentiated  from  chancre,  chancroid  and 
epithelioma.  There  are,  however,  no  essential  features  of  the  diag- 
nosis of  these  conditions  which  differ  from  similar  conditions  found 
on  the  skin. 


GENERAL  SYMPTOMS  121 

GENERAL    SYMPTOMS. 

There  is  nothing  in  the  general  symptoms  of  syphihs  which  may 
be  regarded  as  at  all  pathognomonic.  The  malaise  and  anorexia 
common  early  in  the  course  of  syphilis  are,  as  a  rule,  accompanied 
by  external  manifestations  of  the  disease,  such  as  chancre  and 
lesions  of  the  skin  and  mucous  membranes.  If  these  are  not  present 
and  laboratory  evidence  is  negative,  a  diagnosis  may  be  impossible. 

Syphilitic  fever,  also,  in  the  majority  of  cases  is  accompanied 
by  external  manifestations  of  the  disease.  If  these  are  not  present, 
it  may  rarely  be  necessary  to  differentiate  syphilis  from  malaria. 
This,  as  a  rule,  can  be  done  by  microscopic  examination  of  the  blood 
for  plasmodise  and  by  the  Wassermann "  test,  which  will  almost 
invariably  be  positive  in  syphilis  of  severe  enough  type  to  cause 
fever  simulating  malaria.  It  must  be  remembered,  however,  that 
the  Wassermann  test  may  be  positive  in  malaria  in  the  absence  of 
syphilis  and  it  may  be  necessary  to  resort  to  therapeutic  tests. 

The  other  general  symptoms  of  syphilis,  the  blood  picture,  the 
pulse,  the  respiration,  the  polydipsia  and  the  blood-pressure  present 
little  or  nothing  of  diagnostic  value.     (See  page  104  et  seq.) 


CHAPTER  VII. 
LABORATORY  DIAGNOSIS. 

DEMONSTRATION  OF  TREPONEMA  PALLIDUM. 

Since  the  epoch-making  work  of  Schaudinn  the  diagnosis  of 
syphilis  has  been  very  materially  aided  by  the  demonstration  of 
the  Treponema  pallidum.  While,  as  has  been  pointed  out,  this 
minute  organism  has  be,en  found  in  every  class  of  syphilitic  lesion 
and  in  all  organs  and  tissues  of  the  body,  it  is  in  the  chancre  that  it 
is  most  searched  for,  for  diagnostic  purposes.  This  is  because  at 
this  time  other  manifestations  usually  are  absent  and  no  one  could 
make  a  positive  diagnosis  of  syphilis  without  the  finding  of  the 
infecting  organism.  It  is  of  the  utmost  importance  to  make  a 
search  for  the  treponema  in  all  suspicious-looking  sores,  because, 
if  found,  and  it  should  be  in  a  very  large  percentage  of  uncompli- 
cated chancres,  treatment  may  be  instituted  at  once  and  a  cure 
accomplished  in  a  comparatively  short  period. 

In  the  later  manifestations  of  syphilis  other  means  of  diagnosis 
are  much  more  frequently  resorted  to,  and,  usually,  with  more 
satisfactory  results.  However,  occasionally  it  is  desirable  to  look 
for  Treponema  pallidum  in  papules  (this  was  the  lesion  in  which 
they  were  first  found),  in  condylomata,  in  enlarged  glands,  and 
even  in  the  blood. 

The  most  frequently  used  methods  for  the  demonstration  of 
the  organism  of  Schaudinn  are  dark-field  illumination,  staining  of 
smears,  the  so-called  India-ink  method,  and  staining  sections  of 
tissue.  Inoculation  experiments  which  have  been  described  in 
Chapter  III  are  too  uncertain  and  consume  too  much  time  to  be 
of  much  value  in  diagnosis. 

Collection  of  Material. — When  material  is  to  be  collected  from  a 
chancre  for  examination  by  the  first  three  methods  mentioned,  no 
caustic  or  antiseptic  should  be  used  for  at  least  twenty-four  hours. 
As  the  chancre  is  usually  situated  on  a  very  sensitive  portion  of  the 
body,  it  should  be  handled  with  as  much  gentleness  as  possible  to 
avoid  unnecessary  pain.  It  should  first  be  cleansed  thoroughly 
with  soap  and  water,  rinsed  and  dried.  This  procedure  will  free  the 
area  of  the  majority  of  Spirocheta  refringens  and  to  a  certain  extent 
of  other  contaminating  organisms.  It  may  now  be  possible  to 
squeeze  a  drop  of  clear  serum  from  the  lesion,  especially  if  it  be 


DEMONSTRATION  OF   TREPONEMA   PALLIDUM  123 

ulcerated.  If  no  serum  exudes,  it  will  be  necessary  to  puncture  the 
sore,  which  should  be  done  at  the  edge.  As  more  treponemata 
usually  lie  deeply  embedded  in  the  lesion  than  superficially  it  is 
desirake  to  remove  the  outer  layers  of  epithelium  or  to  pierce 
beneath  them.  The  edge  of  the  sore  may  be  punctured  by  a  Hage- 
dorn  needle,  a  scapel,  or  it  may  be  scraped  with  a  small  curette 
or  similar  instrument.  Sometimes  it  is  sufficient  to  rub  the  lesion 
with  a  piece  of  gauze.  When  the  area  is  now  squeezed  a  few  drops 
of  blood  will  usually  exude  which  should  be  removed  with  a  piece  of 
gauze  or  absorbent  cotton.  Pressure  should  be  continued  until  a 
drop  of  clear  or  faintly  pink  serum  is  obtained.  This  may  be  taken 
up  with  a  platinum  loop,  a  capillary  pipette,  or  directly  on  a  slide 
or  cover-glass  by  touching  it  to  the  lesion.  Stitt^  has  recommended 
the  introduction  of  a  capillary  pipette  beneath  the  epidermis  and 
aspirating  a  drop  of  fluid  from  the  deeper  layers  of  the  chancre. 

Similar  methods  of  procedure  are  employed  in  collecting  material 
for  examination  from  papules,  condylomata,  and  mucous  patches. 

In  obtaining  material  from  an  enlarged  gland  the  area  over  the 
gland  should  first  be  sterilized  with  alcohol  or  tincture  of  iodin. 
A  small  hypodermic  needle  on  an  all-glass  syringe  is  now  plunged 
into  the  gland.  If  the  gland  moves  with  the  needle,  it  is  proof  that 
the  needle  is  within  the  gland.  The  latter  is  held  steady  with  the 
fingers  of  one  hand  while  the  point  of  the  needle  is  moved  about 
within  its  substance,  after  which  as  much  as  possible  of  the  gland 
juice  is  aspirated,  and,  after  removal  of  the  needle,  forced  out  into 
a  watch-glass  or  other  suitable  receptacle. 

When  it  is  desirable  to  examine  the  blood  for  the  organism  of 
syphilis,  1  or  2  c.c.  should  be  withdrawn  by  venipuncture  and 
diluted  with  ten  times  its  volume  of  a  0.1  per  cent,  solution  of 
acetic  acid,  centrifugalized  thoroughly,  and  smears  made  of  the 
sediment. 

It  should  seem  hardly  necessary  to  sound  a  note  of  warning 
against  infection  during  these  procedures,  yet  the  author  has  seen 
one  case  of  chancre  of  the  finger  probably  due  to  carelessness  in 
collecting  syphilitic  material  for  examination. 

Dark-field  Illumination. — This  method  of  procedure  is  without 
question  by  far  the  most  satisfactory  for  demonstrating  Treponema 
pallidum,  as  the  organisms  may  in  this  way  be  seen  alive  and  in  the 
actively  motile  state. 

The  apparatus  for  dark-field  illumination  consists  of  (a)  a  special 
condenser  which  replaces  the  ordinary  substage  condenser  of  any 
good  microscope,  (6)  a  rubber  funnel  stop  which  is  screwed  into 
the  oil-immersion  objective  just  beneath  the  lens,  (c)  a  powerful 

1  U.  S.  Nav.  Med.  Bull.,  1914,  viii,  p.  242. 


124  LABORATORY  DIAGNOSIS 

light,  such  as  a  small  arc  lamp,  with  a  biconvex  lens,  (d)  slides 
of  a  suitable  thickness,  generally  about  1  mm.,  and  (e)  especially 
thin  cover-glasses  (not  more  than  0.17  mm.).  The  condenser  is  so 
constructed  that  the  central  rays  of  light  from  the  mirror  of  the 
microscope  are  blocked  out  by  means  of  an  opaque  stop,  while  the 
peripheral  rays  are  reflected  from  the  paraboloidal  sides  of  the 
condenser  and  strike  solid  objects  in  the  specimen  at  a  very  oblique 
angle.  After  leaving  the  top  of  the  condenser  the  rays  pass  unre- 
fracted  to  a  sharp  focus,  which  should  be  on  the  upper  surface  of  the 
slide.  In  order  to  bring  this  about  there  must  be  a  drop  of  cedar 
oil,  or  distilled  water,  placed  upon  the  upper  surface  of  the  condenser 
to  keep  the  rays  from  refracting,  and  further,  the  slide  must  be  of 
suitable  thickness  for  the  condenser  employed.  At  least  it  must 
be  no  thicker,  or  the  rays  will  come  to  a  focus  between  the  surfaces 
of  the  slide. 

After  coming  to  a  focus  on  the  upper  surface  of  the  slide,  the 
rays  of  light  which  meet  no  obstruction  pass  on  to  the  cover-glass, 
and  if  a  dry  objective  is  being  employed  they  now  are  reflected 
from  the  upper  surface  and  are  lost.  With  an  oil-immersion  objec- 
tive, which  has  been  stopped  down  with  the  rubber  funnel  so  that 
the  numerical  aperture  is  less  than  1,  the  rays  pass  on  but  are  not 
taken  up  by  the  objective.  The  result,  as  can  readily  be  seen, 
will  be  darkness  which  makes  the  dark  field.  The  rays  of  light  which 
meet  with  some  obstruction. on  the  upper  surface  of  the  slide,  such 
as  bacteria,  blood  cells  or  treponemata  are  reflected  upward  into 
the  objective  and  are  seen  as  bright  objects  on  a  dark  background. 

Technic. — After  replacing  the  ordinary  substage  condenser  of 
the  microscope  with  the  dark-field  condenser  the  lamp  is  placed 
some  30  to  50  cms.  distant,  and  so  adjusted  that  the  beam  of  light 
is  thrown  forward  and  completely  fills  the  plain  mirror.  With  a  low- 
power  objective  the  upper  surface  of  the  condenser  is  viewed,  and 
by  means  of  the  centring  screws  the  small  circle  engraved  on  its 
upper  surface  is  brought  into  the  centre  of  the  field.  A  drop  of 
cedar  oil,  or  better,  distilled  water,  is  now  placed  on  the  upper 
surface  of  the  condenser  and  the  latter  is  lowered  a  few  millimeters. 

The  slide,  which  should  be  perfectly  clean,  is  now  prepared  by 
placing  on  it  a  drop  of  the  serum  which  has  been  collected,  as  de- 
scribed above,  and  carefully  lowering  a  cover-glass  over  it,  avoiding 
the  forming  of  air  bubbles.  Should  the  drop  of  serum  be  too  small 
to  fill  the  space  between  the  slide  and  the  cover-glass,  or  if  it  con- 
tains too  much  blood,  a  drop  of  salt  solution  should  be  added. 
Occasionally  there  is  so  much  blood  that  even  by  adding  the  salt 
solution  so  many  corpuscles  remain  in  the  field  that  the  dark- 
ground  effect  is  largely  destroyed.  The  author  has  overcome  this 
difficulty  by  adding,  instead  of  the  salt  solution,  a  drop  of  0.1  per 


DEMONSTRATION  OF  TREPONEMA   PALLIDUM  125 

cent,  acetic  acid,  which  lakes  the  red  corpuscles,  but  at  the  same 
.time  destroys  the  motility  of  the  treponemata. 

The  film  between  the  slide  and  cover-glass  should  be  as  thin  as 
possible  and  should  be  ringed  with  vaselin. 

After  preparing  the  slide  it  is  placed  on  the  stage  of  the  micro- 
scope and  the  condenser  racked  up  into  position.  Great  care  should 
be  exercised  in  raising  the  condenser  that  no  air  bubbles  are  formed 
in  the  oil  or  water  which  is  interposed  between  the  condenser  and 
the  slide.  For  if  such" a  bubble  be  present,  no  matter  how  small, 
the  rays  of  light  meeting  it  are  reflected  upward  and  pass  through 
the  specimen  almost  vertically  and  illuminate  the  whole  field, 
destroying  the  dark-ground  eft'ect. 

If  the  light  has  been  properly  adjusted  and  no  bubbles  are  present, 
either  in  the  specimen  or  in  the  film  between  the  slide  and  condenser, 
a  light  area  should  be  seen  in  the  centre  of  the  cover-glass.  If  it  is 
not  present,  it  may  readily  be  produced  by  manipulating  the  mirror. 
The  specimen  is  now  viewed  with  the  low-power  objective  and  a 
bright  spot  will  be  seen  in  the  centre  of  the  field  when  it  is  in  focus. 
By  manipulations  of  the  condenser  up  and  down  the  bright  spot  is 
reduced  to  the  smallest  size  possible.  The  high-power  objectives 
may  now  be  used.  For  diagnostic  purposes  the  high-power  dry 
objectives  are  more  satisfactory,  while  for  studying  minute  details 
of  the  treponemata  oil-immersion  objectives,  stopped  down  as 
described  above,  should  be  employed. 

The  Treponema  pallida  appear  as  bright,  shining,  motile  spirals 
on  a  dark  background.  Their  extreme  delicacy,  characteristic 
motility,^  and  the  regularity  and  depth  of  the  spirals,  serve  to 
differentiate  them  from  other  organisms  except  Treponema  pertenue, 
Treponema  microdentium,  and  Treponema  mucosum.  It  is  not 
necessary  to  give  much  consideration  to  the  first  of  these  organisms, 
owing  to  the  limited  area  in  which  yaws  is  found.  The  two  other 
organisms,  Treponema  microdentium  and  Treponema  mucosum, 
which,  while  resembling  the  Treponema  pallidum,  are  shorter  and 
thinner  and  are  found  only  in  the  mouth. 

It  may,  however,  be  necessary  to  resort  to  staining  absolutely 
to  differentiate  them,  the  pallidum  staining  with  much  more 
difficulty.  All  other  organisms  which  occur  in  chancres  and  con- 
dylomata, such  as  Spirocheta  balantidium,  Spirocheta  phagedenis, 
Spirocheta  refringens,  and  Spirocheta  gracilis,  may  be  distinguished 
from  Treponema  pallidum  by  their  motility  and  morphology. ' 

It  is  well,  however,  for  the  beginner  to  have  the  distinguishing 
features  of  the  various  organisms  pointed  out  to  him  by  an  experi- 
enced  worker,  or,  at  least,  to  study  carefully  the  treponemata 

1  See  Chapter  III,  p.  34. 


126  LABORATORY  DIAGNOSIS 

from  a  syphilitic  papule,  where  they  occur  free  from  other  organisms, 
or  in  a  preparation  from  a  pure  culture. 

India-ink  Method. — By  this  method,  originally  described  by 
Burri^  for  demonstration  of  bacteria,  a  similar  effect  to  that  of  the 
dark-field  illuminator  is  produced.  It  depends  upon  the  fact  that 
when  India  ink  is  mixed  with  the  material  in  which  are  found  the 
treponemata,  bacteria,  etc.,  these  are  not  penetrated,  and,  there- 
fore, appear  white  upon  a  black  background  when  a  thin  film  is 
made  of  the  mixture. 

A  drop  of  the  material  is  collected  as  described  above,  placed 
on  one  end  of  a  slide,  a  drop  of  the  ink  added  (Gunther-Wagner 
Chin  Chin)  and  with  the  end  of  another  slide  a  film  is  made  in  a 
similar  manner  to  preparing  a  blood  film.  The  film  is  allowed  to 
dry  and  is  examined  with  an  oil-immersion  lens. 

Walters^  has  pointed  out  that  many  makes  of  India  ink  contain 
organisms  which  appear  like  the  treponemata  when  the  ink  alone 
is  smeared  on  the  slide.  To  obviate  this  he  advises  the  use  of  a 
solid  dry  stick  of  India  ink  rubbed  up  in  a  small  mortar  with  a 
few  drops  of  sterile  distilled  water.  The  author  has  found  this 
very  satisfactory.  Another  method  of  obtaining  perfectly  clear 
ink  is  to  centrifugalize  it  thoroughly  before  use. 

The  main  objection  to  the  India-ink  method  is  that  the  trepone- 
mata loose  their  most  distinguishing  characteris-tic,  namely,  their 
motility.  However,  the  fact  remains  that  after  preparing  a  specimen 
in  this  manner  the  Treponema  pallida  maintain  their  spiral  contour 
while  certain  other  similar  organisms  loose  their  formation  to  a 
more  or  less  extent. 

Collargol. — This  silver  compound  has  been  used  as  a  substitute 
for  India  ink,  but  in  the  author's  experience  possesses  no  advantage 
over  the  latter. 

Staining  of  Smears. — The  number  of  methods  described  for  staining 
the  parasite  of  syphilis  is  legion,  but  of  some  half-dozen  tried  by 
the  author  Giemsa's  method  is  unquestionably  the  best. 

The  formula  for  preparing  Giemsa's  stain  is  as  follows : 

Azure  II  eosin 3  grams 

Azure  II 8      " 

Glycerin  (Merk,  c.  p.) 250       " 

Methyl  alcohol  (Kahlbaum) .  250       " 

This  stain  may  be  purchased  prepared  ready  for  use  from  any 
dealer  in  bacteriological  supplies.  For  use  the  stock  stain  is  freshly 
diluted  in  the  proportion  of  one  drop  of  stain  to  one  cubic  centimeter 

1  Centralbl.  f.  BacterioL,  1908,  2  Abth.,  xx,  p.  95. 

2  Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  p.  1666. 


DEMONSTRATION  OF  TREPONEMA   PALLIDUM  127 

of  water,  and  to  this  is  added  one  drop  of  potassium  carbonate 
(1  to  1000)  to  each  cubic  centimeter. 

Great  care  is  needed  in  preparing  the  film  for  staining.  The 
slide  or  cover-glass  should  be  perfectly  clean  and  free  from  grease. 
Further,  the  film  should  be  spread  as  thinly  as  possible,  and  this 
may  be  accomplished  satisfactorily  in  a  manner  similar  to  pre- 
paring a  blood  film.  If  the  film  is  too  thick,  the  organisms  will  not 
take  the  stain  well,  and  also,  a  deposit  of  the  stain  is  likely  to  occur 
which  will  interfere  greatly  with  finding  the  parasites.  After 
drying  in  the  air  the  films  are  fixed  in  absolute  alcohol  for  fifteen  to 
twenty  minutes,  and  stained  with  the  diluted  stain  for  forty-five 
minutes  to  one  hour.  They  are  then  washed  with  distilled  water, 
blotted  with  filter  paper,  and  if  on  cover-glasses  mounted  in  Canada 
balsam. 

By  this  method  the  Treponema  pallidum  usually  appears  as  thin, 
rose-colored  spirals,  while  the  Spirocheta  refringens  and  other 
similar  organisms  are  colored  violet.  This,  however,  cannot  be 
used  as  an  absolutely  distinguishing  feature,  as  it  is  by  no  means 
constant. 

Goldhorn's  Stain. — This  stain  has  the  advantage  of  being  much 
more  rapid  than  Giemsa's,  but,  owing  to  the  difficulty  in  manu- 
facturing it,  variations  occur  which  make  it  less  reliable. 

The  method  of  preparation  is  as  follows:  Dissolve  1  gram  of 
lithium  carbonate  in  200  c.c.  of  distilled  water.  Add  2  grams  of 
methylene  blue,  heat  carefully,  filter,  and  divide  into  two  parts. 
Add  5  per  cent,  acetic  acid  to  one  part  until  it  is  acid  to  litmus  and 
then  mix  with  the  other  part.  After  this  add  a  weak  solution  of 
erosin  until  a  pale  blue  color  is  obtained.  Let  stand  for  twenty-four 
hours  and  then  filter  oft'  the  precipitate  which  forms,  and  dry 
without  heat.  Dissolve  1  gram  of  powder  in  100  c.c.  of  absolute 
methyl  alcohol.  Smears  are  fixed  in  methyl  alcohol  fifteen  minutes 
and  the  stain  applied  five  to  ten  minutes.  The  specific  organisms 
appear  a  violet  color. 

Jenner's  Stain. — While  most  of  the  Romanowsky  stains  will 
demonstrate  the  Treponema  pallidum  fairly  well,  Jenner's  modi- 
fication is  one  of  the  best  for  this  purpose. 

The  staining  fluid  is  prepared  by  dissolving  5  grams  of  the 
powdered  stain,  which  is  an  eosinate  of  methylene  blue,  in  100  c.c. 
of  absolute  methyl  alcohol.  Smears  are  first  fixed  one  minute  in 
methyl  alcohol  and  stained  five  to  ten  minutes.  They  should  be 
kept  covered  air-tight  and  free  from  water. 

Staining  Sections  of  Tissue. — While  the  organism  of  syphilis  may 
be  demonstrated  quite  readily  in  sections  of  luetic  tissue,  this 
method  is  not  of  much  diagnostic  importance,  owing  to  the  time 
consumed  in  preparing  the  sections.    It  has,  however,  added  much 


128  LABORATORY  DIAGNOSIS 

to  our  knowledge  concerning  the  location  of  the  Treponema  pallidum 
in  various  syphilitic  lesions,  and  very  materially  strengthened  its 
position  as  the  causative  agent. 

At  first  the  greatest  difficulty  was  encountered  in  staining  the 
treponemata  in  sections.  Bertarelli  and  Volpino^  applied  Van 
Ermenghem's  method  of  staining  cilia  to  cut  sections  with  fairly 
good  results.  However,  by  this  method  it  is  very  difficult  to  keep 
a  precipitate  of  metallic  silver  from  being  deposited  upon  the 
specimen. 

A  great  advance  was  made  by  Levaditi,^  who  adapted  Ramon-y- 
Cajal's  method  of  staining  nerve  fibrils.  By  this  method  the  tissues 
are  stained  en  bloc  instead  of  in  sections.  The  original  method  of 
Levaditi  consists  of  impregnating  the  tissues  with  silver  nitrate  and 
subsequently  reducing  the  silver  with  pyrogallic  acid. 

Later,  in  conjunction  with  Manouelian,  Levaditi^  changed  the 
proceeding  somewhat,  and,  while  it  is  slightly  more  complicated, 
better  results  are  obtained,  especially  with  tissue  removed  from 
the  living  body. 

The  details  of  the  technic  are  as  follows: 

1.  Fix  small  pieces  of  tissue  (1  to  2  mm.  in  thickness)  in  10  per 
cent,  formalin  (4  per  cent,  formaldehyde)  twenty-four  hours. 

2.  Dehydrate  in  96  per  cent,  alcohol  twelve  to  twenty-four  hours. 

3.  Wash  in  distilled  water  until  tissue  sinks  to  the  bottom  of 
the  containing  vessel. 

4.  Place  in  a  tightly  stoppered  bottle  in  a  1  per  cent,  solution 
of  silver  nitrate  in  distilled  water,  to  which  has  been  added  just 
before  use  10  per  cent,  of  pyridin.  A  considerable  quantity  of  this 
solution  should  be  used  and  the  tissue  allowed  to  remain  in  it  at 
room  temperature  two  or  three  hours,  and  then  at  a  temperature 
of  50°  C.  four  to  six  hours.  The  permiability  of  the  tissue  will 
determine  the  length  of  time  for  it  to  remain  in  this  solution. 

5.  Wash  rapidly  in  a  10  per  cent,  solution  of  pyridin. 

6.  Place  for  reduction  in  a  4  per  cent,  solution  of  pyrogallic  acid, 
to  which  is  added  just  before  use  10  per  cent,  of  pure  acetone  and 
15  per  cent,  of  the  total  volume  of  pyridin.  Reduction  will  be 
completed  in  two  or  three  hours. 

7.  Dehydrate  in  graded  alcohols  as  follows:  30  per  cent.,  50 
per  cent.,  70  per  cent.,  85  per  cent,,  95  per  cent.,  and  absolute, 
allowing  tissue  to  remain  two  or  three  hours  in  each. 

8.  Clear  in  xylol  until  tissue  sinks. 

9.  Immerse  in  melted  paraffin  at  52°  C.  (melting-point  50°  C.) 
three  changes,  one-half  hour  each. 

1  Rivista  d'Igiene,  1905;  Centralbl.  f.  Bacteriol.,  1906,  xli,  p.  74. 

2  Compt.  rend.  Soc.  de  biol.,  1905,  lix,  p.  326. 

3  Ibid.,  1906,  p.  134. 


DEMONSTRATION  OF   TREPONEMA   PALLIDUM  129 

10.  Block  in  paraffin  and  cool  rapidly  by  immersion  in  cold 
water. 

11.  Section  (sections  should  not  be  thinner  than  5  microns). 

12.  Attach  sections  to  slide  with  Mayer's  glycerin-albumin 
mixture.  (Equal  parts  of  egg-white  and  glycerin,  well  beaten  and 
filtered  through  paper,  plus  a  small  amount  of  phenol  as  a  pre- 
servative.) 

13.  Heat  over  flame  just  sufficiently  to  melt  paraffin. 

14.  While  still  warm  place  in  xylol  a  few  seconds. 

15.  Mount  in  balsam. 

The  treponemata  are  stained  an  intense  black  with  the  silver 
nitrate  and  stand  out  most  distinctly  from  the  surrounding  tissues. 
Some  authorities  advocate  counter-staining  the  sections  with 
various  agents  to  bring  out  more  distinctly  the  cellular  structure 
of  the  tissues.  The  author  has  not  found  this  necessary,  as  the 
relation  of  the  treponemata  to  the  tissues  is  sufficiently  evident 
without  this  precedure. 

Paretic  Brain  Tissue. — Many  investigators  attempted  to  demon- 
strate the  Treponema  pallidum  in  the  brains  of  paretics  without 
success  until  Noguchi  and  Moore^  accomplished  this  feat.  In  their 
original  article  these  authors  fail  to  describe-  their  technic,  stating 
that  a  modified  Levaditi  method  was  employed.  However,  in  a 
later  communication  by  Noguchi,^  the  technic  is  described  as 
follows : 

Specimens  5  to  7  mm.  in  thickness  are  cut  from  the  gyri  frontali, 
gyri  recti,  or  any  other  region,  and  hardened  in  10  per  cent,  formalin. 
Noguchi  states  that  specimens  which  have  remained  in  formalin 
at  least  one  year  give  best  results,  owing  to  the  fact  that  the  formalin 
interferes  with  the  staining  of  the  neuroglia  fibrils  and  accelerates 
the  staining  of  the  treponemata.  From  the  formalin  the  specimens 
are  removed  to  a  mixture  containing  10  per  cent,  formalin,  10  per 
cent,  pyridin,  25  per  cent,  acetone,  25  per  cent,  alcohol,  and  30 
per  cent,  aqua  destillata,  in  which  they  are  permitted  to  remain 
for  five  days  at  room  temperature.  Following  this  they  are 
thoroughly  washed  in  distilled  water  for  twenty -four  hours.  Next 
they  are  transferred  to  96  per  cent,  alcohol  for  three  days  and  again 
washed  in  distilled  water  for  twenty-four  hours.  The  specimens 
are  now  treated  as  follows,  using  a  dark  bottle  as  a  container: 

1.  Bath  in  15  per  cent,  silver  nitrate  solution  for  three  days  at 
37°  C.  (or  five  days  at  room  temperature), 

2.  Reduce  in  4  per  cent,  pyrogallic  acid  solution  with  the  addition 
of  5  per  cent,  formalin  for  twenty-four  hours  at  room  temperature. 

3.  Wash  thoroughly  in  distilled  water. 

1  Jour.  Exper.  Med.,  1913,  xvii,  p.  232. 

2  Jour.  Cutan.  Dis.,  1913,  xxxi,  p.  543. 


130  LABORATORY  DIAGNOSIS 

4.  Transfer  to  80  per  cent,  alcohol  for  twenty-four  hours. 

5.  Transfer  to  95  per  cent,  alcohol  for  three  days. 

6.  Absolute  alcohol  for  two  days. 

7.  Xylol,  xylol-paraffin,  paraffin. 

Sections  should  be  cut  3  to  5  microns  in  thickness. 

Noguchi  advises  the  impregnation  of  other  treponemata  con- 
taining tissue  at  the  same  time  as  control. 

If  the  staining  is  successful,  the  various  tissues  will  vary  in  color 
from  a  pale  yellow  to  a  yellowish  brown,  while  the  specific  organisms 
are  a  distinct  black. 

COMPLEMENT-FIXATION  TESTS. 

Principles. — The  principle  of  complement-fixation  was  discovered 
by  Bordet  and  Gengou^  in  1901,  but  it  was  not  until  1906  that 
Wassermann,  Neisser,  and  Bruck^  utilized  this  phenomenon  for  the 
diagnosis  of  syphilis.  Since  that  time  this  method,  almost  uni- 
versally known  as  the  Wassermann  reaction,  has  been  studied  and 
modified  by  many  investigators  and  hps  developed  into  one  of  the 
most  valuable  clinical  laboratory  tests  of  all  time. 

When  the  animal  body  is  subjected  to  an  infecting  agent, 
substances,  known  as  antibodies,  which  combat  the  infecting  agent 
and  which  are  present  normally  to  a  varying  extent,  are  formed 
within  the  organism.  Antibodies  are  also  formed  when  the  animal 
body  is  injected  with  various  foreign  proteins,  either  organized, 
as  living  or  dead  bacteria,  or  unorganized,  as  egg  albumen.  The 
substances  injected  are  known  as  antigen  and  the  antibodies  pro- 
duced are  of  various  kinds  and  are  known  as  agglutinins,  pre- 
ciintins,  lysins,  etc.  It  is  with  the  latter  antibodies  that  we  have 
to  deal  in  the  complement -fixation  tests. 

It  has  long  been  known  that  the  blood  of  an  animal  of  one  species 
cannot  be  transfused  into  an  animal  of  another  s'pecies  without 
danger  of  fatal  results.  The  reason  for  this  was  shown  to  be  that 
the  blood  of  the  first  animal  contained  certain  substances  which 
destroys  the  red  blood  corpuscles  of  the  second  animal.  These 
substances,  or  antibodies,  which  belong  to  the  class  of  lysins  and 
are  therefore  known  as  hemolysins,  are  normally  ptesent  in  nearly 
all  blood,  or  rather  in  the  serum  of  nearly  all  blood. 

It  was  discovered  by  Bordet  and  Gengou^  that  if  the  corpuscles 
of  an  animal  of  one  species  be  injected  into  an  animal  of  another 
species,  in  doses  small  enough  not  to  injure  the  animal  injected, 
the  serum  of  the  latter  animal  develops  to  a  remarkable  extent  the 

1  Ann.  de  I'Inst.  Pasteur,  1901,  xv,  p.  289. 

2  Deut.  med.  Wchnschr.,  1906,  xxxii,  p.  745. 

3  Ann.  de  I'Inst.  Pasteur,  1901,  xv,  p.  289. 


COMPLEMENT-FIXATION  TESTS  131 

property  of  destroying  or  hemolyzing  the  corpuscles  of  an  animal 
of  the  first  species.  That  is,  while  the  serum  of  the  guinea-pig 
normally  possesses  comparatively  little  hemolyzing  power  for  the 
erythrocytes  of  the  rabbit,  if  a  guinea-pig  be  injected  intraperito- 
neally  with  a  few  small  doses  of  rabbit  erythrocytes  his  serum  soon 
acquires  the  ability  to  hemolyze  quickly  and  completely  rabbit 
corpuscles,  that  is,  hemolysins  are  developed. 

It  was  further  found  that  this  property  of  hemolysis  was  soon 
lost  by  the  serum  on  standing,  or  could  quickly  be  removed  by  heat, 
and  that  it  was  restored  by  the  addition  of  fresh  normal  serum. 
The  phenomenon  of  hemolysis  therefore  depends  upon  two  sub- 
stances, one  resisting  heat  or  thermostabile,  and  present  to  a  slight 
extent  in  nearly  all  normal  sera,  but  capable  of  being  greatly 
increased  by  the  injection  of  specific  erythrocytes,  the  other  easily 
destroyed  by  heat,  or  ihermolabile  and  present  in  all  normal  sera, 
although  to  a  variable  extent,  and  incapable  of  being  increased  by 
injection. 

These  two  substances  have  received  various  names,  but  the  ones 
by  which  they  are  most  frequently  known  are  those  given  them  by 
Ehrlich,  viz.,  amboceptor^  for  the  theromostabile  substance,  and 
complement-  for  the  thermolabile  substance. 

Neither  amboceptor  nor  complement  acting  alone  can  produce 
hemolysis,  nor  can  the  antibody  or  amboceptor  produced  by  infec- 
tion, either  accidental  or  experimental,  produce  lysis  of  the  infecting 
organism  without  complement,  which,  as  stated,  is  present  in  all 
normal  sera.  The  mechanism  of  the  phenomenon  of  lysis  is  believed 
to  be  that  of  a  simple  chemical  action,  the  amboceptor  acting  as  a 
connecting  link  between  the  cells  or  antigen  (bacteria  or  erythro- 
cytes) and  the  complement.  The  action  of  the  amboceptor  is 
specific,  that  is,  it  will  unite  with  only  one  kind  of  cell,  while  comple- 
ment is  thought  to  act  with  any  amboceptor  to  produce  lysis 
(Bordet).  When  these  three  factors  (antigen,  amboceptor,  and 
complement)  are  brought  together  in  the  proper  proportions  the 
complement  is  bound  or  fixed  tightly  to  the  amboceptor  and  none 
is  left  free  in  the  serum.  This  is  the  phenomenon  of  complement- 
fixation. 

When  working  with  the  various  organized  antigens,  such  as 
bacteria  and  erythrocytes,  it  is  easy  enough  to  demonstrate  the 
combination  of  the  amboceptor  and  complement  with  the  antigen, 
that  is,  the  fixation  of  the  complement.  For  example,  a  suspension 
of  red  corpuscles  in  normal  salt  solution  presents  an  orange-red, 
opaque  appearance,  while  after  specific  amboceptor  and  comple- 
ment have  been  added,  and  hemolysis  has  taken  place,  the  color  is 

1  Called  substance  sensibilisatrice  by  Bordet  and  fixateur  by  Metchnikoff. 

2  Called  alexin  by  Bordet  and  cytase  by  Metchnikoff. 


132  LABORATORY  DIAGNOSIS 

seen  to  have  changed  to  a  cherry  red  and  the  solution  is  perfectly 
clear.  But  if  the  antigen  be  unorganized,  such  as  an  extract  of 
bacteria,  the  demonstration  of  the  fixation  of  complement  becomes 
more  difficult.  The  difficulty  is  overcome,  however,  by  adding 
to  the  solution  of  antigen,  amboceptor,  and  complement,  which  has 
stood  for  a  period  sufficiently  long  to  allow  the  fixation  of  the 
complement  to  take  place,  some  red  blood  cells  and  their  specific 
amboceptor.  If  the  complement  has  been  bound,  no  hemolysis 
will  take  place,  as  it  is  impossible  without  complement.  But,  if, 
on  the  other  hand,  the  complement  has  not  been  bound,  hemolysis 
will  occur. 

It  will  readily  be  seen  that  the  presence  of  specific  amboceptor 
or  antibodies  in  the  sera  of  human  beings  may  be  demonstrated  by 
this  method.  In  other  words,  that  various  diseases  may  be  diagnosed 
by  complement-fixation. 

Indeed,  soon  after  the  discovery  of  the  phenomenon  by  Bordet 
and  Gengou  several  investigators  made  use  of  this  method  for  the 
diagnosis  of  typhoid  fever,  tuberculosis,  meningitis,  etc.  The 
antigen  employed  by  Wassermann  and  Bruck^  was  an  extract  of 
cultures  of  the  bacteria  in  sterile  distilled  water. 

Wassermann  was  apparently  early  struck  with  the  thought  of 
diagnosing  syphilis  by  complement-fixation,  but  was  confronted 
with  the  difficulty  of  being  unable  at  that  time  to  cultivate  the 
infecting  organism,  the  Treponema  pallidum.  He,  however,  soon 
conceived  the  idea  of  utilizing  the  liver  of  a  fetus,  dead  of  congenital 
syphilis,  which  is  particularly  rich  in  treponemata,  for  the  prepara- 
tion of  his  antigen.  Only  fourteen  days  after  the  publication  of 
their  technic  by  Wassermann,  Neisser  and  Bruck,  Detre,^  working 
independently,  published  a  method  differing  only  in  minor  details 
in  which  he  used  chiefly  an  extract  of  condylomata  as  antigen. 

Before  long  the  whole  medical  world  was  interested  in  the 
"Wassermann  reaction,"  and  many  investigators  attempted  to 
improve  and  simplify  it. 

In  the  original  technic  Wassermann,  Neisser  and  Bruck  used  a 
watery  extract  of  syphilitic  fetal  liver  as  antigen.  This  was  found 
by  most  investigators  to  be  very  unstable,  although  Citron^  thinks 
this  due  to  carelessness  in  handling.  However,  as  congenital 
syphilitic  livers  are  comparatively  difficult  to  procure,  it  was  soon 
evident  that  in  order  to  make  the  test  practical  some  other  method 
of  preparing  antigen  must  be  found. 

Michaelis^  preserved  the  liver  of  a  syphilitic  fetus  in  the  frozen 

1  Med.  Klinik,  1905,  i,  p.  1409. 

2  Wien.  klin.  Wchnschr.,  1906,  xix,  p.  619. 

3  Immunity,  Philadelphia,  1912,  p.  162. 
^Berl.  klin.  Wchnschr.,  1907,  xliv,  p.  1103. 


COMPLEMENT-FIXATION   TESTS  133 

state,  while  Marie  and  Levaditi/  after  pulverizing  it,  dried  it  in 
vacuo  to  preserve  it. 

The  first  real  step  in  advance,  however,  was  made  when  it  was 
discovered  that  alcoholic  extracts  of  syphilitic  liver  were  capable 
of  acting  as  antigen. ^  It  was  not  long,  also,  before  a  number  of 
investigators  found  that  the  alcoholic  extracts  of  normal  organs  of 
man  and  animals  possessed  considerable  antigenic  value.^  It  was 
therefore  proved  that  the  complement-fixation  test  for  syphilis 
was  not  altogether,  at  least,  a  true  antigen-antibody  reaction. 

Many  other  methods  of  preparing  antigens  have  been  devised 
and  the  more  important  ones  will  be  dealt  with  later. 

In  the  original  technic  Wassermann,  Neisser  and  Bruck  heated 
the  patient's  serum  which  was  to  be  examined  to  destroy  the  native 
complement.  This  process,  known  as  inactivation,  is  followed  by 
most  serologists  today. 

Normal  guinea-pig  serum  was  used  as  complement  while  the 
sheep-rabbit  hemolytic  system  was  employed  to  demonstrate  the 
fixation  of  complement.  That  is,  sheep's  corpuscles  and,  as  ambo- 
ceptor the  serum  of  a  rabbit  injected  with  sheep's  corpuscles,  were 
used. 

While,  as  stated  above,  most  serologists  use  inactivated  patient's 
serum  in  the  complement-fixation  test  for  syphilis,  some  have 
employed  a  non-inactivated  serum.  Thus  Noguchi^  uses  non- 
inactivated  serum  but  in  such  small  quantities  (0.02  c.c),  that 
the  native  complement  may  be  ignored.  He  also  used  guinea- 
pig  serum  for  complement  but  the  human-rabbit  hemolytic  system 
instead  of  the  sheep  system. 

Bauer^  also  proposed  the  use  of  a  non-inactivated  serum,  but 
utilized  the  normal  anti-sheep  amboceptor  in  the  serum  being 
tested,  instead  of  adding  sheep-rabbit  amboceptor.  He,  of  course, 
used  sheep's  corpuscles. 

Hecht®  went  still  further  and  relied  upon  the  native  complement 
of  the  patient's  serum  as  well  as  the  natural  anti-sheep  amboceptor. 

Other  investigators  used  other  hemolytic  systems.  Thus, 
Detre^  used  the  horse-rabbit  hemolytic  system,  Boas^  used  the 
goat-rabbit  system,  Browning^  the  ox-rabbit  system,  and  Jobling^" 
the  hen-rabbit  system. 

1  Ann.  de  I'lnst.  Pasteur,  1907,  xxi,  p.  138. 

2  Plaut:  The  Wassermann  Sero  Diagnosis  of  Syphilis  in  its  Application  to  Psy- 
chiatry, New  York,  1911,  p.  11. 

3  Ibid. 

*  Serum  Diagnosis  of  Syphilis,  second  edition,  Philadelphia  and  London,  1911, 
p.  59. 

'  Cited  by  Noguchi,  ibid.,  p.  39. 

6  Wien.  klin.  Wchnschr.,  1909,  xxii,  p.  265.  '  Ibid.,  1906,  xix,  p.  619. 

8  Cited  by  Noguchi,  Serum  Diagnosis  of  Syphilis,  second  edition,  Philadelphia 
and  London,  1911,  p.  41. 

9  Ibid.  1°  Personal  communication. 


134  LABORATORY  DIAGNOSIS 

Technic. — Preparation  of  Reagents.  Patient's  Serum. — ^The 
patient's  serum  may  be  obtained  in  a  variety  of  ways.  Noguchi^ 
collects  the  blood  in  a  Wright's  capsule  after  puncturing  with  a 
Hagedorn  needle  the  ventral  side  of  the  last  joint  of  the  middle 
finger.  The  blood  is  allowed  to  clot  at  room  temperature  and  the 
serum  drawn  off  with  a  capillary  pipette.  This  method  will  suffice 
when  Noguchi's  technic  for  the  performance  of  the  test  is  to  be 
employed,  where  only  small  quantities  of  serum  are  needed,  but 
is  not  to  be  recommended  when  larger  amounts  of  serum  are  desired. 

Some  workers  prick  the  finger  or  lobe  of  the  ear  and  "milk"  the 
blood  into  a  sterile  test-tube.  To  the  author's  mind  this  is  a  most 
barbarous  method  and  has  nothing  to  commend  it. 

Probably  the  most  frequently  used  method  of  collecting  blood, 
and  also  one  of  the  most  satisfactory,  especially  for  amateurs,  is 
by  puncture  of  one  of  the  veins  of  the  elbow  with  a  hypodermic 
needle  attached  to  an  all-glass  syringe  of  sufficient  capacity.  A 
20-  to  25-gauge  needle  may  be  used  with  success,  while  a  5  c.c.  Luer 
syringe  is  very  satisfactory.  The  pain  is  slight  and  a  sufficient 
quantity  of  blood  may  be  collected  in  a  minimal  period  of  time. 

A  rubber  tourniquet  is  placed  around  the  arm  just  above  the 
elbow,  the  patient  requested  to  close  and  open  the  fist  two  or  three 
times,  when,  in  thin  individuals,  the  veins  usually  will  stand  out 
prominently.  If  they  are  not  prominent,  a  little  snapping  with  the 
finger  will  sometimes  render  them  so.  In  fleshy  individuals  the 
veins  are  sometimes  so  obscure  that  they  cannot  be  seen  but  may 
be  palpated,  and  occasionally,  in  extremely  fleshy  persons,  even 
palpation  does  not  reveal  their  presence.  Sometimes,  if  it  is  impos- 
sible to  demonstrate  a  vein  at  the  elbow,  one  on  the  back  of  the  hand 
or  at  the  ankle  may  be  utilized. 

The  site  of  the  puncture  should  be  sterilized  by  rubbing  it  with 
a  little  alcohol  or  painting  it  with  iodin  and  the  needle  inserted 
in  the  direction  of  the  blood  stream.  Successful  venepuncture  can 
only  be  accomplished  by  having  a  sharp  needle  and  by  keeping  the 
vein  steady.  In  fleshy  individuals  the  latter  is  accomplished  by 
the  perivascular  tissues,  but  in  thin  persons  the  vein  must  be 
steadied  by  the  operator.  The  author  has  found  that  this  can 
best  be  accomplished  by  encircling  the  arm  of  the  patient  with  the 
thumb  and  middle  finger  of  the  left  hand  and  drawing  the  skin 
taut  over  the  vein.  If  the  plunger  of  the  syringe  does  not  fit  too 
snugly  when  the  vein  is  punctured,  the  blood  will  flow  into  the 
syringe.  Care  must  be  exercised  not  to  pierce  the  posterior  wall 
of  the  vein.  Traction  may  then  be  exerted  on  the  plunger  until  a 
sufficient  quantity  of  blood  is  collected.     The  tourniquet  is  loosened, 

1  Serum  Diagnosis  of  Syphilis,  second  edition,  Philadelphia,  1911,  p.  54. 


COMPLEMENT-FIXATION  TESTS  135 

the  needle  removed  and  a  piece  of  sterile  cotton  or  gauze  pressed 
tighth'  over  tlie  puncture  wound  and  held  by  an  assistant  or  by 
the  patient  himself.  If  the  patient  is  told  to  elevate  the  arm  over 
the  head,  there  usually  will  be  no  ecchymosis,  which  may  occur  if 
this  is  not  done. 

The  blood  is  placed  in  a  sterile  test-tube  and  allowed  to  clot  at 
room  temperature.  In  about  fifteen  minutes  clotting  will  have 
occurred  and  the  separation  of  the  serum  progressed  to  a  sufficient 
degree  that  centrifugalization  will  cause  the  clot  to  be  forced  to 
the  bottom  of  the  tube  and  the  serum  may  be  poured  or  pipetted 
off.  The  author  sterilizes  small  test-tubes  (15  mm.  X  10  cm.)  for 
this  purpose  by  boiling  them  for  fifteen  minutes  in  normal  salt 
solution. 

After  this  sterilization  the  blood  rarely  becomes  contaminated 
and  much  more  serum  can  be  collected  than  by  using  test-tubes 
sterilized  by  dry  heat.  If  it  is  desirable  to  use  the  blood  imme- 
diately after  collection,  it  may  be  placed  in  a  centrifuge  tube  and 
centrifugalized  at  a  very  high  speed  for  several  minutes  when  the 
clear  plasma  may  be  pipetted  off. 

Some  authors^  advocate  collecting  blood  by  puncturing  a  vein 
with  a  needle  and  allowing  the  blood  to  run  through  a  rubber  tube 
into  a  test-tube  without  the  use  of  a  syringe.  This  is  very  satis- 
factory, except  that  a  larger  needle  must  be  used  and  more  skill  is 
required,  and,  further,  if  many  specimens  are  collected  the  cleaning 
and  sterilizing  of  the  needles  entail  considerable  labor. 

A  very  convenient  method  of  collecting  blood  by  venepuncture 
is  by  the  use  of  a  Keidel  tube.  This  apparatus  consists  of  a  sealed 
vacuum  ampule,  over  the  small  end  of  which  is  slipped  a  short  piece 
of  rubber  tubing  attached  to  a  needle.  When  the  needle  is  inserted 
into  a  vein  and  the  neck  of  the  ampule  within  the  rubber  tubing 
broken,  the  vacumn  creates  suction  and  draws  the  blood  into  the 
ampule.  The  main  objection  to  these  tubes  are  their  expense,  and 
also,  that  if  the  needle  is  not  within  the  vein  when  the  neck  of  the 
ampule  is  broken  the  vacuum  will  be  destroyed  without  collecting 
any  blood  and  another  tube  must  be  used. 

A  method  of  collecting  blood  has  been  devised  by  the  author, 
which,  to  his  mind,  overcomes  all  objections.  The  apparatus  is 
shown  in  Figs.  42  and  43. 

A  special  platinum  needle  is  employed  which  has  a  square  "  collar" 
firmly  attached  to  it,  as  shown  in  the  illustration.  A  platinum 
needle  is  used  because  it  may  be  quickly  and  absolutely  sterilized 
by  placing  in  a  Bunsen  flame  for  a  few  seconds.  Further,  the  blood 
will  not  clot  as  rapidly  in  such  a  needle  as  in  a  steel  needle.     The 

1  Kaplan:  Serology  of  Nervous  and  Mental  Diseases,  Philadelphia,  1914,  p.  52. 


136 


LABORATORY  DIAGNOSIS 


reason  for  this  is  probably,  as  Kolmer^  suggests,  that  the  bore  of 
the  platinum  needle  is  smoother,  and  perhaps  also  that  there  is 
some  direct  biological  influence  exerted  upon  the  process  of  coagu- 
lation. The  needle  is  caught  at  the  collar  with  a  pair  of  artery 
forceps  which  have  had  their  tips  bent  at  a  right  angle,  the  collar 
protecting  the  needle  from  being  dented.  A  sterile  test-tube  of 
convenient  size  is  placed  in  the  right  angle  of  the  forceps  so  that 
the  proximal  end  of  the  needle  projects  into  its  mouth,  and  is  held 
against  the  forceps  either  by  a  rubber  band  or  by  the  right  hand  of 
the  operator.  A  tournequet  is  placed  around  the  arm  of  the  patient 
in  the  usual  way,  and  after  sterilizing  the  area  the  needle  is  thrust 


Fig.  42 


Fig.  43 
Figs.  42  and  43. — Author's  apparatus  for  collecting  blood. 


into  one  of  the  veins  of  the  elbow,  the  forceps  holding  it  steady  and 
furnishing  a  convenient  handle.  The  blood  usually  will  flow  in 
a  stream  and  5  or  6  c.c.  may  be  collected  in  a  very  few  seconds. 
By  holding  the  needle  under  running  water  the  blood  will  be 
washed  out  and  it  may  be  resterilized .  A  19-gauge  needle  is  best 
for  ordinary  purposes,  but  different  sizes  may  be  used  as  occasion 
demands. 

In  very  young  children  it  sometimes  is  desirable  to  puncture 
the  external  jugular  vein  or  one  of  the  veins  of  the  scalp,  although  a 
very  satisfactory  method  of  collecting  blood  from  such  patients  is 

^  Personal  communication. 


COMPLEMENT-FIXATION  TESTS 


137 


by  cupping.  An  area  of  the  back  is  cleansed  by  rubbing  with 
alcohol,  after  which  a  few  superficial  linear  incisions  are  made. 
A  sterile  cup  is  applied  and  a  sufficient  quantity  of  blood  usually 
flows  into  the  cup,  from  which  it  may  be  emptied  into  a  sterile  test- 
tube.  This  method  may  be  applied  to  exceedingly  fleshy  individuals 
when  it  is  impossible  to  demonstrate  a  vein. 

The  blood  of  the  patient  should  not  be  collected  during  the 
process  of  active  digestion,  as,  if  collected  at  that  time,  the  serum 
will  sometimes  be  quite  "milky"  in  appearance.  This  milkiness 
does  not  interfere  with  the  reaction  except,  perhaps,  to  obscure 
slightly  the  end-results. 


Collecting  blood  with  author's  apparatus. 


If  kept  perfectly  sterile,  syphilitic  sera  will  retain  their  comple- 
ment-fixation properties  for  several  months,  except  that  they  may 
develop  so-called  anticomplementary  bodies,  which  usually  may  be 
removed  by  heating  to  55°  C.  for  thirty  minutes.  Normal  sera 
also  develop  anticomplementary  bodies  on  standing,  but  from  these 
sera  also  they  usually  may  be  removed  by  the  process  of  inactivation. 

Antigens. — Wassermann's  Original. — The  liver  of  a  congenitally 
syphilitic  fetus  is  weighed  and  cut  into  small  pieces.  To  this  is 
added  four  times  its  weight  of  0.5  per  cent,  phenol  solution  in  normal 
saline.  The  mixture  is  placed  in  a  brown  bottle  and  shaken  with 
a  shaking  apparatus  for  twenty-four  hours.  Following  this  it  is 
centrifugalized  until  the  larger  pieces  of  liver  settle  to  the  bottom 
of  the  tubes,  leaving  the  supernatant  fluid  slightly  turbid.  The 
latter  is  poured  off  into  a  brown  bottle  and  placed  in  the  ice-box, 


138  LABORATORY  DIAGNOSIS 

where,  after  a  few  days  of  sedimentation,  it  assumes  a  yellowish- 
brown  color  and  is  ready  for  use.  It  should  be  kept  in  the  ice-box, 
and  when  it  is  to  be  used  only  a  sufficient  quantity  is  carefully 
poured  off  without  disturbing  the  sediment.  Aqueous  extracts 
are  used  but  little  today  and  are  to  be  considered  more  of  historical 
interest  than  of  practical  value. 

Alcoholic  Extract  of  Syphilitic  Liver. — This  antigen,  which  is  one 
of  the  most  extensively  used,  is  prepared  by  mincing  finely  a 
syphilitic  fetal  liver,  then  adding  to  it  absolute  ethyl  alcohol  in 
the  proportion  of  10  c.c.  of  alcohol  to  each  gram  of  tissue.  The 
mixture  may  be  shaken  in  a  shaking  apparatus  for  twenty-four 
hours  and  then  placed  in  an  incubator  at  37°  C.  and  allowed  to 
remain  for  ten  days.  Or,  if  a  shaking  machine  is  not  available, 
it  may  be  placed  in  the  incubator  at  once,  in  which  case  it  should 
be  allowed  to  remain  a  few  days  longer.  The  containing  vessel 
should  be  tightly  stoppered  to  prevent  evaporation.  After  having 
remained  in  the  incubator  a  sufficient  length  of  time  it  is  filtered 
through  a  fat-free  filter  paper,  or  one  washed  with  ether  and  alcohol, 
which  removes  any  hemolytic  substances  which  may  be  present. 
The  filtrate,  which  is  the  antigen,  is  collected  and  stored  in  a  tightly 
stoppered  bottle  in  the  ice-box.  The  sediment  which  forms  after 
the  antigen  has  stood  for  a  few  days  should  not  be  removed  or 
disturbed.  The  alcoholic  extract  of  luetic  fetal  liver  has  been  the 
standard  antigen  with  the  majority  of  workers  for  years  and  is  to 
be  recommended  highly. 

Alcoholic  Extracts  of  Normal  Organs. — ^Human,  guinea-pig,  and 
beef  heart  or  liver  may  be  employed,  and  the  process  of  preparing 
the  antigen  is  the  same  as  that  described  for  the  alcoholic  extracts 
of  syphilitic  liver.  Care  should  be  exercised  not  to  include  any 
fat  in  the  mixture.  Of  the  alcoholic  extracts  of  normal  organs 
that  of  guinea-pig  heart  seems  to  give  the  best  results. 

Cholesterinized  Antigens. — These  antigens  are  prepared  by  adding 
0.4  per  cent,  of  pure  cholesterin  to  alcoholic  extract  of  normal 
human,  beef  or  guinea-pig  heart.  The  cholesterin  is  not  readily 
soluble  in  the  alcohol,  so  it  should  be  permitted  to  stand  for  about 
one  week,  when  it  may  again  be  filtered  and  stored  in  tightly  stop- 
pered bottles.  After  a  time  a  slight  sediment  usually  forms  which 
should  not  be  disturbed. 

Sachs^  was  the  first  to  use  cholesterin  reinforced  heart  extracts 
as  antigen. 

Mcintosh  and  Fildes^  next  employed  this  antigen  and  reported 
very  favorably  upon  its  use. 


1  Berl.  klin.  Wchnschr.,  1911,  xlviii,  p.  2066. 

2  Ztschr.  f.  Chemotherapie,  1912,  1,  p.  79. 


COMPLEMENT-FIXATION  TESTS  139 

The  work  of  Walker  and  Swift/  which  was  very  comprehensive, 
showed  conclusively  the  value  of  the  cholesterinized  antigens, 
especially  the  reinforced  human  heart  extracts,  and  soon  a  number 
of  investigators'^  reported  series  of  cases  in  which  it  had  been  used 
with  great  satisfaction.  It  was  found  to  be  more  sensitive  than 
any  antigen  yet  produced,  giving  more  positive  results  in  known 
specific  cases,  and  by  most  investigators  found  not  to  give  positive 
results  in  known  negative  cases. 

Thomas  and  Ivy,^  however,  decried  the  use  of  cholesterinized 
antigens,  claiming  that  many  positive  results  were  obtained  by  them 
in  non-syphilitic  cases.  Their  observations  have  not  been  con- 
firmed, except  that  perhaps  an  occasional  slightly  positive  reaction 
may  be  obtained,  upon  which  with  any  antigen  (except  Treponema 
pallidum  extracts),  and  in  the  absence  of  clinical  symptoms,  no 
one  would  make  a  positive  diagnosis  of  syphilis. 

Acetone-insohihh  Lipoids. — Noguchi*  devised  this  method  of 
preparing  antigen,  which  is  as  follows :  The  heart,  liver  or  kidney 
of  a  man,  beef,  guinea-pig,  rabbit  or  dog  is  finely  minced  and  mixed 
with  10  parts  of  absolute  alcohoP  and  extracted  for  several  days 
at  37°  C.  After  filtration  through  paper  the  filtrate  is  evaporated 
to  dryness  by  the  use  of  an  electric  fan.  The  residue  is  taken  up 
with  a  sufficient  quantity  of  ether  and  placed  in  a  tightly  stoppered 
receptacle  and  kept  overnight  in  a  cool  place.  The  turbidity  will 
now  be  seen  to  have  cleared  up  by  the  settling  of  the  insoluble 
particles  to  the  bottom.  The  clear  supernatant  fluid  is  carefully 
decanted  off,  and  placed  in  a  clean  beaker.  The  author  has  found 
it  most  convenient  to  place  the  etherial  solution  in  a  separatory 
funnel,  as,  after  the  insoluble  particles  have  settled  to  the  bottom, 
they  may  be  drawn  oft'  by  opening  the  stop-cock,  leaving  the  clear 
solution.  The  latter  is  now  condensed  to  a  small  quantity  by 
evaporating  off  the  ether,  after  which  the  concentrated  solution  is 
mixed  with  10  volumes  of  pure  acetone. 

A  light  brownish  precipitate  is  formed,  which  soon  settles  to  the 
bottom  of  the  vessel.  After  decantation  of  the  supernatant  fluid 
the  precipitate  becomes  a  sticky  mass,  which  may  be  stored  in 
this  form,  or  it  may  be  dissolved  in  ether  in  the  proportion  of 
0.3  gram  to  1  c.c.  and  mixed  with  9  volumes  of  pure  methyl  alcohol. 
This  is  the  antigen  and  should  be  stored  in  tightly  stoppered  bottles 
in  a  cool  place.     Noguchi  claims  for  this  antigen  that  it  is  more 

1  Jour.  Exper.  Med.,   1913,  xviii,  p.  75. 

2  Jour.  Am.  Med.  Assn.,  1914.  Ixii,  p.  1458;  Jour.  Michigan  Med.  Soc,  1914, 
viii,  p.  421;  Arch.  Int.  Med.,  1914.  xiv,  p.  563. 

3  Jour.  Am.  Med.  Assn.,  1914.  Ixii,  p.  363. 

^  Serum  Diagnosis  of  Syphilis,  second  edition,  Philadelphia  and  London,  1911, 
p.  79. 

^  The  author  has  used  95  per  cent,  alcohol  with  excellent  results. 


140  LABORATORY  DIAGNOSIS 

sensitive  than  any  other,  owing  to  the  fact  that  by  its  use  non- 
inactivated  sera  may  be  employed. 

Trepo7iema  Pallidum  Antigens. — Aqueous  or  alcohoHc  extracts  of 
pure  cultures  of  Treponema  pallidum  may  be  employed  as  antigen. 

Noguchi^  prepared  an  aqueous  extract  as  follows :  Several  strains 
of  treponemata  should  be  used  and  tubes  containing  good  growths, 
cultivated  after  the  method  described  by  Noguchi,  are  selected. 
The  oil  is  poured  off,  the  tube  filed  and  broken  just  above  the  tissue, 
and  the  agar  column  removed.  The  upper  or  uninfected  portion  is 
cut  off  and  discarded  and  the  remainder  is  ground  by  shaking  with 
marbles  and  a  sufficient  quantity  of  normal  saH  solution  in  a  seal- 
able  porcelain  jar  in  a  shaking  apparatus  until  the  treponemata 
are  disintegrated.  The  emulsion  is  transferred  to  a  sterile  bottle, 
heated  to  60°  C.  for  thirty  minutes  and  0.4  per  cent,  phenol  added. 

Alcoholic  extracts  were  prepared  by  Craig  and  Nichols''^  by  mix- 
ing the  treponemata  containing  agar  with  ten  times  its  weight  of 
absolute  alcohol  and  extracting  for  ten  days  with  frequent  shaking. 
Following  the  extraction  the  mixture  is  filtered  and  the  filtrate 
evaporated  to  one-third  its  volume. 

Noguchi  found  that  the  aqueous  extracts  gave  a  positive  reaction 
in  certain  cases  of  treated  syphilis  or  in  those  in  which  the  infection 
has  existed  for  a  long  time  without  symptoms  when  the  lipoidal 
antigen  was  negative  or  faintly  positive.  He  thinks  that  the  value 
of  the  pallidum  extracts  is  as  a  "gauge  for  the  defensive  activity 
of  the  infected  host." 

Craig  and  Nichols,  using  their  alcoholic  extracts  of  Treponema 
pallidum,  found  17  sera  gave  the  same  results  as  the  alcoholic 
extracts  of  syphilitic  liver,  4  gave  weaker  reactions,  6  stronger,  and 
4  gave  positive  reactions  where  the  liver  antigen  gave  negative 
reactions.  But  of  20  sera  which  gave  positive  reactions  with  the 
liver  antigen  7  gave  negative  reactions  with  the  pallidum  antigen. 

These  investigators  also  showed  that  positive  reactions  could 
be  obtained  in  syphilitics  with  antigens  prepared  by  cultures  of 
Spirocheta  pertenuis  and  Spirocheta  microdentia,  although  usually 
weaker  than  those  obtained  with  the  Treponema  pallidum 
antigen. 

The  Author's  Antigen. — ^A  normal  human  heart  is  removed  at 
autopsy  with  aseptic  precautions  as  soon  after  death  as  possible. 
The  muscular  portion,  avoiding  all  fat  and  connective  tissue,  is 
ground  in  a  sterile  meat  grinder  and  mixed  with  absolute  alcohol 
in  the  proportion  of  10  grams  to  100  c.c.  The  mixture  is  placed 
in  a  sterile  tightly  stoppered  jar  and  extracted  at  37°  C.  for  two 
weeks.     The  jar  should  be  shaken  thoroughly  several  times  daily. 

1  Jour.  Am.  Med.  Assn.,  1912,  Iviii,  p.  1163. 

2  Jour.  Exper.  Med.,  1912,  xvi,  p.  336. 


COMPLEMENT-FIXATION  TESTS  141 

Following  the  extraction,  to  the  filtrate  is  added  0.4  per  cent,  of 
pure  cholesterin.     After  standing  about  one  week  it  is  again  filtered. 

Several  strains  of  Treponema  pallidum  are  grown  in  large  quan- 
tities and  sedimented  after  the  method  of  Zinnser,  Hopkins  and 
Gilbert/  and  extracted  and  filtered  in  a  manner  similar  to  that 
described  for  the  extraction  of  the  sterile  human  heart.  The  two 
extracts  are  mixed  in  equal  proportions  and  stored  in  tightly  stop- 
pered bottles  in  a  cool  place.  The  reason  for  preparing  the  antigen 
with  aseptic  precautions  is  to  avoid  including  extracts  of  contami- 
nating microorganisms  which  might  lead  to  false  binding  of  com- 
plement. This  undoubtedly  has  sometimes  been  the  case  with 
extracts  of  old  syphilitic  fetal  liver. 

Complement. — While,  as  stated  above,  all  normal  sera  contain 
complement  in  variable  amounts,  it  has  been  found  that  the  serum 
of  the  guinea-pig  is  best  suited  for  the  piu-pose  of  supplying  com- 
plement for  the  Wassermann  reaction.  Large,  healthy  animals 
should  be  selected  and  should  not  be  used  during  the  process  of 
active  digestion,  as  the  serum  of  blood  collected  at  this  time  may 
be  quite  "milky"  in  appearance.  While  this  does  not  interfere 
with  the  complemental  properties  of  the  serum,  it  does  somewhat 
obscure  the  reaction.  The  blood  may  be  collected  by  severing 
the  carotid  arteries  with  a  quick  slash  of  a  sharp  knife  and  allowing 
it  to  flow  into  a  large  Petri  dish  or  other  receptacle  in  w^hich  it  is 
allowed  to  clot  and  the  serum  collected. 

This  is  an  unnecessary  sacrifice  of  pigs,  as  from  5  to  10  c.c.  of 
blood  may  be  withdrawn  with  a  hypodermic  needle  and  syringe 
from  the  heart  of  a  good-sized  animal  without  killing  him,  and  in 
two  weeks  he  may  be  bled  again.  The  author  has  removed  blood 
in  this  manner  eight  to  ten  times  at  intervals  of  two  or  three  weeks 
from  large,  healthy  animals. 

The  pig  should  be  etherized,  the  hair  of  the  precordia  clipped, 
and  the  site  wiped  with  a  little  alcohol  or  touched  with  iodin.  A 
19-gauge,  1-inch  needle  is  most  satisfactory,  and  a  10  c.c.  Luer 
syringe  may  be  used.  The  pulsations  of  the  heart  can  usually  be 
seen  and  can  always  be  felt.  The  thorax  of  the  pig  should  be 
steadied  with  the  left  hand  and  the  needle  thrust  through  the  chest 
wall  and  into  the  pulsating  heart,  care  being  exercised  not  to  pierce 
the  rear  wall.  When  the  point  of  the  needle  is  well  within  the 
chamber  (ventricle)  of  the  heart  the  blood  will  usually  be  seen  to 
rise  and  fall  in  the  syringe  with  the  pulsations.  Slight  traction 
should  now  be  exerted  on  the  plunger  and  from  5  to  10  c.c.  of  blood 
slowly  withdrawn.  This  should  be  placed  in  test-tubes  which  have 
been  prepared  by  boiling  in  normal  salt  solution,  as  described  for 

1  Jour.  Exper.  Med.,  1915,  xxi,  p.  213. 


142 


LABORATORY  DIAGNOSIS 


the  preparation  of  tubes  for  patient's  serum.  After  about  one  hour 
the  clot  will  have  formed  and  partial  separation  of  the  serum 
occurred,  when  the  tubes  may  be  centrifugalized  and  the  serum 
poured  or  pipetted  off  into  a  sterile  tube  and  placed  in  the  ice-box. 
The  tubes  containing  the  blood  should  also  be  placed  in  the  ice-box, 
as  more  serum  will  separate  off  on  standing.  While  absolute 
asepsis  in  collecting  guinea-pig  serum  for  complement  is  not  impera- 
tive, the  author  considers  it  well  to  use  reasonable  aseptic 
precautions.  Aher  emptying  the  syringe  of  blood  it  should  be 
filled  with  warm  sterile  normal  salt  solution  and  injected  intra- 
peritoneally  into  the  pig.  The  author  has  found  that  by  following 
this  procedure  a  considerably  greater  number  of  pigs  survive  than 
by  not  following  it. 


Fig.  45. — Method  of  bleecliug  guinea-pig  for  complement. 

In  small  serological  laboratories  the  problem  of  securing  guinea- 
pig  serum  for  complement  is  one  of  more  or  less  seriousness,  and 
where  only  a  few  tests  are  made  at  a  time,  a  considerable  quantity 
of  complement  may  be  lost  owing  to  its  rapid  deterioration.  Com- 
plement may  be  frozen  and  preserved  at  a  low  temperature  ( — 15° 
C.)  for  several  months,  but  most  small  laboratories  are  not  equipped 
for  such  procedures. 

Austin^  advocated  making  a  40  per  cent,  dilution  of  the  guinea-pig 
serum  with  25  per  cent,  sodium  chloride  solution.  Then,  in  his 
tests  he  used  0.6  per  cent,  salt  solution  instead  of  the  usual  0.9 
per  cent,  and  states  that  by  so  doing  he  gets  approximately  0.9 
per  cent,  in  his  tubes. 


1  Jour.  Am.  Med.  Assn.,  1914,  Ixii,  p.  868. 


COMPLEMENT-FIXATION  TESTS  143 

In  order  to  secure  accuracy  of  diJution  as  well  as  to  seciu-e  a  suit- 
able dilution  for  titration  the  following  technic  has  been  devised 
by  the  author  and  is  now  used  in  his  laboratory: 

An  8.1  per  cent,  sodium  chloride  solution  is  prepared  and  auto- 
claved. 

Fresh  guinea-pig  seriun  is  diluted  with  this  solution  1  to  1,  and 
sealed  in  small  tubes,  2  c.c.  to  the  tube.  It  will  be  seen  that  each 
tube  contains  1  c.c.  of  pm-e  guinea-pig  serum  containing  (supposedly) 
0.9  per  cent,  of  sodium  chloride  or  0.009  gram,  and  1  c.c.  of  an  S.l 
per  cent,  sodimn  chloride  or  0.081  gram.  The  entire  sodimn 
chloride  content  of  each  tube  is  0.09  gram,  corresponding  to  the 
quantity  each  10  c.c.  of  normal  salt  solution  should  contain.  There- 
fore, in  order  to  make  a  solution  containing  0.9  per  cent,  sodimn 
chloride  it  is  only  necessary  to  add  8  c.c.  of  distilled  water  to  the 
contents  of  each  tube,  and  1  to  10  dilution  of  guinea-pig  serum  is 
produced. 

It  is  the  custom  in  the  author's  laboratory  to  bleed  from  the  heart 
three  to  five  good-sized  guinea-pigs  at  one  time,  secm-ing  from  20 
to  50  c.c.  of  blood,  which  lasts  from  ten  days  to  two  weeks, 
depending  upon  the  nmnber  of  tests  being  made.  \Miile  the 
complement  usually  is  not  kept  longer  than  two  weeks,  some  six 
weeks  old  has  been  used  and  was  apparently  as  active  as  ever. 

Amboceptor. — The  amboceptor  of  the  hemolytic  system  used  for 
the  complement-fixation  test  for  syphilis  must,  of  coiu-se,  correspond 
to  the  erythrocytes  employed.  That  is,  if  sheep's  corpuscles  are 
used,  the  amboceptor  must  be  anti-sheep  immmie  sermn  prepared 
by  injecting  an  animal  of  some  other  species  with  sheep  cells. 
While  the  rabbit  is  usually  employed  for  this  pmpose  the  author 
has  been  able  to  produce  a  very  good  anti-hiunan  amboceptor  by 
administering  intravenously  large  doses  (as  much  as  30  c.c.)  of 
human  erythrocytes  to  a  goat. 

The  blood  for  administration  should  be  collected  aseptically. 
If  the  sheep  is  used  the  wool  should  be  clipped  from  the  side  of  the 
neck,  a  toiu-nequet  placed  around  it  as  low  down  as  possible,  when 
the  external  jugular  vein  will  stand  out  prominently.  Usually 
not  more  than  20  or  30  c.c.  of  blood  are  desired,  and  thisamoimt  is 
best  collected  in  a  large  sterile  Luer  s\Tinge,  or  a  trocar  may  be 
introduced  and  the  blood  allowed  to  run  into  the  collecting  vessel. 

In  either  case  the  blood  should  be  placed  in  a  sterile  tiask  con- 
taining a  fevv'  glass  beads,  in  which  it  should  be  shaken  for  several 
minutes  to  "whip"  out  the  fibrin  and  prevent  clotting.  After  this 
it  should  be  poured  into  sterile  centrifuge  tubes  and  centrifugalized 
at  a  high  rate  of  speed  until  the  corpuscles  have  settled  to  the  bottom 
of  the  tubes  and  the  clear  serum  remains  on  top.  This  should  be 
carefully  pipetted  oft'  without  distiu-bing  the  corpuscles  and  the 


144  LABORATORY  DIAGNOSIS 

tubes  filled  with  sterile  normal  salt  solution  (0.85  per  cent.).  This 
should  be  mixed  with  the  corpuscles  with  a  sterile  glass  rod  or  by 
drawing  the  mixture  up  into  a  sterile  pipette  and  forcing  it  out 
several  times. ^ 

The  tubes  should  again  be  centrifugalized  until  the  corpuscles  are 
forced  to  the  bottom  and  the  fluid  above  is  perfectly  clear,  when  it 
should  be  removed  and  replaced  with  more  salt  solution.  This 
process,  known  as  "washing  the  corpuscles,"  is  for  the  purpose  of 
removing  all  traces  of  serum  and  should  be  repeated  four  or  five 
times.  The  reason  for  removing  the  serum  is  that  if  it  is  left  other 
antibodies,  than  hemolysins,  such  as  precipitins,  will  be  formed  in 
the  body  of  the  injected  animal  and  interfere  with  the  reaction. 
After  thorough  washing  of  the  corpuscles  they  are  made  up  with 
normal  salt  solution  to  the  volume  which  existed  before  pipetting 
off  the  serum. 

Either  intraperitoneal  or  intravenous  irjections  may  be  made, 
although  anaphylaxis  often  results  from  the  latter  method.  How- 
ever, ether  administered  to  an  animal  suffering  from  anaphylactic 
shock  will  usually  overcome  the  symptoms,  saving  the  animal. 

Intraperitoneal  Injections. — If  the  intraperitoneal  method  is 
chosen  the  hair  should  be  clipped  and  shaved  from  the  belly  of  a 
large,  preferably  male,  rabbit.  The  animal  is  held  by  an  assistant 
in  a  vertical  position  with  the  head  down  and  the  hind  legs  up. 
This  causes  the  intestines  to  gravitate  toward  the  diaphragm, 
making  their  puncture  by  the  needle  less  likely.  The  site  of  injec- 
tion should  be  painted  with  iodin  and  the  cells  slowly  injected  by 
means  of  a  syringe  and  needle.  A  good  amboceptor  is  not  always 
produced,  and  the  amount  of  corpuscles  injected  and  the  number 
and  frequency  of  the  injections  do  not  seem  to  bear  a  constant 
relation  to  the  quality  of  the  amboceptor.  The  author  has  usuaUy 
been  able  to  produce  a  satisfactory  amboceptor  by  injecting  4,  8, 
12,  16,  and  20  c.c.  of  blood  with  four-  or  five-day  intervals  and 
bleeding  the  rabbit  on  the  ninth  or  tenth  day  after  the  last  injection. 

Simon^  recommends  the  injection  of  the  washed  corpuscles  of 
30  c.c.  of  blood  on  two  occasions  seven  days  apart,  and  bleeding 
the  rabbit  from  nine  to  eleven  days  after  the  latter  injection.  This 
method  has  not  proved  satisfactory  in  the  hands  of  the  author. 

Intravenous  Injections.— The  marginal  vein  of  the  ear  of  the  rabbit 
is  chosen  as  the  best  one  for  injection.  A  considerable  area  over 
the  vein  should  be  shaved  and  wiped  with  alcohol.  An  assistant 
holds  the  animal,  blindfolding  the  eyes  with  one  hand  and  compress- 

1  The  author  has  found  that  when  the  corpuscles  are  to  be  injected  immediately, 
and  they  should  be,  they  may  be  mixed  with  the  salt  solution  by  placing  the  thumb 
over  the  mouth  of  the  tube  and  inverting  several  times. 

2  Manual  of  Clinical  Diagnosis,  Philadelphia  and  New  York,  1911,  p.  143. 


COMPLEMENT-FIXATION  TESTS 


145 


ing  the  vein  near  the  root  of  the  ear  with  the  thumb  and  forefinger 
of  the  other  hand.  The  reason  for  bHndfolding  the  eyes  is  that  when 
this  is  done  the  rabbit  generally  offers  no  resistance.  The  com- 
pression of  the  vein  will  usually  cause  it  to  become  distended 
sufficiently  to  allow  the  introduction  of  a  small  needle.  A  22-  or 
23-gauge  needle  should  be  used  with  a  5  c.c.  liUer  syringe,  and  the 
corpuscles  should  be  drawn  up  into  the  syringe  through  the  needle, 
not  poured  into  it,  to  avoid  particles  of  fibrin  getting  into  the 
mixture  and  clogging  the  needle.  The  injections  should  be  made 
slowly. 

A  very  satisfactory  amboceptor  usually  may  be  produced  by 
injecting  2,  3,  3,  4,  and  4  c.c.  of  corpuscles  four  or  five  days  apart 
and  bleeding  on  the  ninth  or  tenth  day  following  the  last  injection. 
The  author  prefers  the  intravenous  method,  as  less  blood  is  required, 
although  it  is  slightly  more  dangerous  to  the  rabbit. 


Fig.  46. — Intravenous  injection  of  rabbit  for  amboceptor. 


On  the  ninth  day  following  the  last  injection  of  corpuscles, 
whether  the  intraperitoneal  or  intravenous  route  has  been  employed, 
a  small  quantity  of  blood  should  be  drawn  from  the  rabbit,  allowed 
to  clot,  and  the  serum  tested  for  its  hemolytic  properties.  Blood 
for  this  purpose  is  best  removed  from  one  of  the  marginal  ear 
veins  in  a  manner  similar  to  the  injection  of  the  corpuscles,  except 
that  a  smaller  needle  should  be  used  (25-  or  26-gauge),  and  the  needle 
directed  against  the  blood  stream;  1  or  2  c.c.  may  be  removed  in 
this  manner.  If  the  serum  shows  a  sufficiently  strong  hemolytic 
activity,  the  rabbit  may  either  be  bled  from  the  heart  in  a  manner 
similar  to  that  described  for  the  bleeding  of  guinea-pigs  for  com- 
plement, or  after  etherizing  the  carotid  artery  may  be  dissected 
10 


146  LABORATORY  DIAGNOSIS 

out,  a  cannula  inserted,  and  the  blood  collected  in  sterile  containers, 
allowing  the  animal  to  bleed  to  death. 

In  either  case  the  blood  should  be  placed  in  tubes  sterilized  by 
boiling  in  normal  salt  solution.  These  are  allowed  to  stand  for 
two  or  three  hours  at  room  temperature  and  then  placed  in  the 
ice-box  overnight.  The  next  morning  the  serum  may  be  poured 
or  pipetted  off,  that  which  is  perfectly  clear  being  placed  in  a  test- 
tube  and  that  containing  blood  in  a  centrifuge-tube  and  centri- 
fugalized  until  clear. 

The  serum  may  be  preserved  by  adding  10  per  cent,  of  a  5  per 
cent,  phenol  solution,  or  50  per  cent,  of  pure  glycerin,  after  inacti- 
vation  at  55°  C.  for  thirty  minutes. 

Corpuscle  Suspension. — The  corpuscle  suspension  for  the  hemo- 
lytic system  may  be  prepared  by  collecting  the  blood  in  a  sterile 
flask  and  shaking  with  glass  beads,  as  described  under  the  Prepara- 
tion of  Amboceptor,  and  the  proper  dilution  made.  Or  a  small 
quantity  of  blood  may  be  collected  in  a  tube  of  sodium  citrate 
solution  (20  per  cent,  in  normal  saline),  which  prevents  clotting 
and  centrifugalized  at  once,  the  corpuccles  washed  as  in  the  other 
method,  and  the  proper  dilution  made. 

Technic  of  Performing  the  Test. — ^Wassermann's  Method. — Before 
the  actual  performing  of  the  test  the  amboceptor  must  be  titrated  to 
determine  its  strength.  Aseptic  technic  is  enjoined.  A  series  of 
test-tubes  is  prepared  by  placing  in  each  1  c.c.  of  a  1  :  10  dilution 
of  fresh  guinea-pig  serum  (0.1  c.c.  pure  serum),  1  c.c.  of  a  5  per 
cent,  solution  of  washed  sheep's  cells,  increasing  amounts  of  anti- 
sheep  serum,  and  making  the  whole  amount  up  to  5  c.c.  with  normal 
salt  solution.  The  tubes  are  incubated  at  37°  C.  for  two  hours, 
when  the  tube  containing  the  smallest  amount  of  amboceptor  which 
showed  complete  hemolysis  is  determined  and  this  amount  of  ambo- 
ceptor considered  as  one  V7iit. 

The  aqueous  extract  of  syphilitic  fetal  liver,  or  antigen,  must 
also  first  be  titrated  to  determine  the  smallest  amount  which  of 
itself  will  inhibit  hemolysis,  that  is,  its  anticomplementary  dose. 
This  is  determined  by  adding  to  a  series  of  test-tubes  increasing 
amounts  of  the  extract,  1  c.c.  of  complement,  2  units  of  ambocep- 
tor, and  1  c.c.  of  corpuscle  suspension,  and  the  whole  made  up  to 
5  c.c.  The  tubes  are  incubated  for  two  hours  at  37°  C.  and  only 
such  extracts  are  used  which  in  a  dose  of  0.4  c.c.  do  not  interfere 
with  hemolysis.  It  must  also  be  determined  that  in  considerably 
larger  doses  (0.8  c.c.)  the  extract  of  itself  will  not  hemolyze  the  dose 
of  corpuscles. 

Three  tubes  are  used  for  each  serum  tested,  three  each  for  the 
positive  and  negative  control  sera,  and  three  tubes  for  control  of 
the  hemolytic  system. 


COMPLEMENT-FIXATION   TESTS  147 

Into  the  first  tube  of  each  serum,  including  the  positive  and 
negative  sera,  is  placed  1  c.c.  of  a  1  to  5  dilution  of  antigen  and  into 
the  second  0.5  c.c;  the  third  tube  receives  no  antigen.  The  first 
and  third  tubes  receive  0.2  c.c.  of  inactivated  serum  and  the  second 
0.1  c.c.  Each  tube,  including  the  first  two  of  the  hemolytic  system 
control  tubes,  receives  1  c.c.  of  the  diluted  guinea-pig  serum,  and 
the  total  amount  made  up  to  3  c.c.  The  tubes  are  now  incubated 
for  one  hour  at  37°  C,  after  which  2  units  of  amboceptor,  diluted 
so  that  each  cubic  centimeter  contains  two  units,  and  1  c.c.  of  the 
corpuscle  suspension  are,  added  to  each  tube,  except  the  last  two 
tubes  of  the  hemolytic  system  control,  to  each  of  which  are  added 
1  c.c.  of  salt  solution  and  1  c.c.  of  curpuscle  suspension.  The 
incubation  is  now  continued  for  two  hours,  when  the  tubes  are 
placed  in  the  ice-box  overnight.  The  following  morning  the  results 
are  read  as  follows:  If  tubes  1  and  2  of  a  serum  show  complete 
inhibition  of  hemolysis  the  corpuscles  have  settled  to  the  bottom, 
and  the  fluid  above  being  perfectly  clear  and  free  of  color,  the 
reaction  is  strongly  positive  and  designated,  +  +  +  +  •  If  tube 
1  shows  complete  inhibition  and  tube  2  faint  hemolysis,  the  reaction 
is  designated  +  +  +  •  If  tube  1  shows  complete  inhibition  of 
hemolysis  and  tube  2  complete  hemolysis,  ++  is  recorded,  while 
if  tube  1  shows  partial  hemolysis  and  tube  2  shows  complete 
hemolysis,  the  reaction  is  faintly  positive  and  marked  +•  If  tube 
1  shows  doubtful  binding  of  complement  and  tube  2  shows  com- 
plete hemolysis,  the  reaction  is  doubtful  and  designated  ± .  Com- 
plete hemolysis  in  both  tube  1  and  tube  2  constitutes  a  negative 
reaction  and  is  recorded  — . 

Both  tubes  1  and  2  of  the  negative  control  should  show  complete 
hemolysis,  and  1  and  2  of  the  positive  control  complete  inhibition 
of  hemolysis. 

Tube  3  of  all  sera  should  show  complete  hemolysis  as  no  antigen 
is  placed  in  these  tubes.  Tube  1  of  the  hemolytic  system  control 
tubes  should  show  complete  hemolysis  and  tube  2  and  tube  3 
complete  inhibition. 

Noguchi's  Method. — Aseptic  technic  is  not  necessary,  although 
thorough  chemical  cleanliness  is  prescribed.  Noguchi's  conception 
was  to  so  modify  the  Wassermann  reaction  as  to  place  it  within 
the  hands  of  the  practising  physician.  He  therefore  prescribed  the 
preservation  of  antigen,  amboceptor,  and  complement  by  drying 
on  filter  paper.  This,  however,  except  for  amboceptor,  was  soon 
found  to  be  unsatisfactory  and  was  abandoned. 

As  stated  above,  this  investigator  uses  the  anti-human  hemolytic 
amboceptor,  the  acetone  insoluble  lipoids  as  antigen,  and  the 
patient's  sermn  in  non-inactivated  state.  For  complement  he  uses 
40  per  cent,  solution  of  fresh  guinea-pig  serum  in  normal  saline, 


148  LABORATORY  DIAGNOSIS 

and  his  corpuscle  suspension  consists  of  a  1  per  cent,  solution  of 
washed  human  corpuscles  in  normal  saline. 

The  antigen  and  amboceptor  (either  a  liquid  or  dried  on  filter 
paper)  should  be  titrated  before  use.  The  alcohol  stock  solution 
of  antigen  is  made  into  an  emulsion  by  diluting  1  to  10  with  normal 
salt  solution.  According  to  Noguchi^  an  antigen  is  suitable  for  use 
if  0.4  c.c.  of  this  emulsion  will  not  produce  hemolysis  when  added 
to  the  dose  of  corpuscle  suspension  or  interfere  with  hemolysis  when 
added  to  the  complete  hemolytic  system,  and  will  bind  complement 
with  a  known  luetic  serum  in  a  dose  of  0.2  c.c. 

The  method  of  titrating  amboceptor  is  similar  to  that  described 
under  the  Wassermann  Technic,  except  that  the  amboceptor  is 
dried  on  filter  paper  and  increasing  numbers  of  small  regular  squares 
of  this  are  added  to  the  tubes. 

A  test-tube  rack  having  two  parallel  rows  of  holes  is  secured. 
Two  tubes,  one  in  the  front  row  and  one  in  the  rear  row  of  holes, 
are  used  for  each  serum  to  be  tested  and  two  each  for  positive  and 
negative  controls.     Tubes  10  mm.  X  10  cm.  are  recommended. 

One  drop  from  a  capillary  pipette  of  non-inactivated  serum  is 
placed  in  each  of  the  two  tubes  of  the  test.  (Four  drops  of  inacti- 
vated serum  should  be  used.)  The  positive  and  negative  sera  are 
used  in  like  amounts  or  the  negative  control  tubes  need  contain  no 
serum.  To  each  tube  is  added  0.1  c.c.  of  complement  (40  per  cent, 
guinea-pig  serum),  and  to  the  front  tubes  0.1  c.c.  of  the  antigen 
emulsion.  (If  the  antigen  is  up  to  Noguchi's  standard,  it  will  be 
seen  that  at  least  5  antigenic  units  are  used.)  Finally,  to  each  tube 
is  added  1  c.c.  of  the  corpuscle  suspension.  Incubation  is  carried 
out  for  one  hour  at  37°  C.,  or  for  thirty  minutes  in  a  water-bath 
at  a  like  temperature. 

Following  this  a  slip  of  amboceptor  paper  containing  2  units  is 
added  to  each  tube  and  incubation  continued  for  two  hours,  or 
one  hour  if  the  water-bath  is  used.  The  tubes  are  now  removed 
and  kept  for  two  hours  at  room  temperature,  when  the  results  are 
recorded. 

All  of  the  tubes  in  the  rear  row  should  show  complete  hemolysis 
as  well  as  the  front  tube  of  the  negative  control.  The  front  tube 
of  the  positive  control  should  show  complete  inhibition  of  hemolysis 
and  the  front  tubes  of  the  sera  being  tested  will  indicate  positive 
or  negative,  depending  upon  whether  there  is  hemolysis  or  inhibition. 

Should  any  of  the  rear  tubes  show  partial  or  complete  inhibition 
of  hemolysis  it  is  an  indication  that  anticomplementary  substances 
are  present  in  the  serum.  These  substances  usually  are  thermo- 
labile  and  may  be  destroyed  by  inactivation  at  37°  C.  for  thirty 

1  Serum  Diagnosis  of  Syphilis,  second  edition,  Philadelphia  and  London,  1911, 
p.  83. 


COMPLEMENT-FIXATION   TESTS  149 

minutes  when  the  serum  may  again  be  tested  or  a  fresh  specimen 
secured. 

The  Author's  Method. — The  anti-human  hemolytic  system  is 
employed.  This  system  is  used,  in  the  first  place,  because  of  the 
ease  of  securing  human  blood,  and  in  the  second  place  because  of 
the  fact  that  all  human  sera  contain  to  a  variable  extent  normal 
hemolysins  for  most  foreign  corpuscles.  Of  course,  these  hemo- 
lysins may  be  removed  by  adding  corpuscles  to  the  serum  and 
centrifugalizing.  This  is  a  laborious  process  and  there  is  absolutely 
no  advantage  to  be  gained  in  using  any  other  than  the  human 
hemolytic  system,  therefore  the  author  does  not  recommend  it.  As 
complement,  either  fresh  undiluted  guinea-pig  serum  or  "salted" 
serum  diluted  with  distilled  water  is  used. 

The  patients'  sera  are  used  in  0.1  c.c.  doses  and  should  be  fresh, 
at  least  they  must  be  sterile.  Craig^  has  shown  that  the  contami- 
nation of  normal  sera  by  certain  bacteria  may  cause  the  develop- 
ment of  thermostabile  anticomplementary  substances  which  with 
antigen  cause  inhibition  of  hemolysis.  It  has  also  been  shown 
that  these  substances  may  in  rare  instances  develop  in  sterile 
normal  sera,  but  that  in  this  case  they  also  inhibit  hemolysis  without 
antigen. 

The  corpuscle  suspension  is  a  2  per  cent,  dilution  of  human  cor- 
puscles in  normal  saline.  This  is  best  prepared,  as  practised  in 
the  author's  laboratory,  by  withdrawing  5  or  6  c.c.  of  blood  by 
venepuncture  from  a  patient  whose  serum  is  to  be  tested,  adding 
exactly  2  c.c.  of  it  to  a  centrifuge-tube  of  sodium  citrate  solution 
and  placing  the  remainder  in  a  test-tube  to  clot  for  the  test.  After 
washing  the  corpuscles  three  or  four  times  they  are  made  up  to  50 
c.c.  with  normal  salt  solution,  which  makes  approximately  a  2  per 
cent,  dilution,  as  the  corpuscles  constitute  about  one-half  of  the 
whole  blood.  An  absolutely  accurate  dilution  is  not  essential,  as 
the  same  suspension  is  employed  for  the  test  as  for  titration;  0.5 
c.c.  of  the  suspension  is  used  in  each  tube  and  the  total  volume 
made  up  to  2.5  c.c. 

Since,  as  Noguchi^  has  shown,  the  relation  of  amboceptor  and 
complement  may  be  greatly  varied  within  certain  limits,  it  makes 
no  difference  whether  complement  or  amboceptor  is  titrated  before 
each  test  as  long  as  the  approximate  titer  of  the  other  one  is  known. 
It  is,  of  course,  necessary  to  titrate  each  new  amboceptor  serum 
and  as  it  has  been  found  that  the  pooled  sera  of  two  or  three  guinea- 
pigs  varies  but  little  in  complementary  value,  the  author  has  chosen 
0.1  c.c.  of  guinea-pig  serum  as  the  unit  of  complement  when  titrating 
amboceptor. 

1  Jour.  Exper.  Med.,  1911,  xiii,  p.  521. 

2  Serum  Diagnosis  of  Syphilis,  second  edition,  Philadelphia  and  London,  1911, 
p.  12. 


150  LABORATORY  DIAGNOSIS 

It  will  be  noted  that  the  titration  of  amboceptor  by  the  original 
Wassermann  method  as  well  as  by  the  Noguchi  method  the  unit 
of  amboceptor  is  considered  to  be  the  smallest  amount  which  will 
completely  hemolyze  the  dose  of  corpuscles  in  the  presence  of  0.1 
c.c.  of  guinea-pig  serum.  For  the  actual  performance  of  the  test 
2  units  are  employed.  The  reason  for  employing  2  units  is  that 
all  sera  and  all  antigens  possess  more  or  less  of  anticomplementary 
substance,  so  the  addition  of  the  extra  unit  of  amboceptor  is  deemed 
necessary  to  overcome  these  substances. 

To  the  author's  mind  this  appears  as  an  inaccurate  procedure, 
in  that  the  worker  does  not  know  that  twice  the  amount  of  the 
amboceptor  unit  will  just  produce  hemolysis  in  the  presence  of  a 
negative  serum  and  antigen.  He  also  does  not  know  but  that  when 
a  small  amount  of  complement  is  bound  by  a  slightly  positive 
serum  enough  complement  may  be  left  to  produce  complete  hemo- 
lysis and  a  weakly  positive  test  be  changed  to  a  negative. 

The  Author's  Method  of  Titrating  Amboceptor} — In  order  to 
overcome  these  objections  the  author  adopted  the  following  method 
of  titrating  amboceptor.  Actual  test  conditions  are  imposed 
throughout. 

Fifteen  tubes  are  required  for  the  actual  titration  and  eight  tubes 
for  controls.  These  should  be  chemically  clean,  but  not  necessarily 
sterile.  Into  each  of  the  fifteen  tubes  is  placed  0.1  c.c.  of  known 
negative  inactivated  serum,  or  better  still,  a  like  amount  of  the 
pooled  sera  of  several  known  non-luetic  individuals,  0.1  c.c.  of 
complement,  1  unit  of  previously  titrated  antigen  (diluted  so  that 
1  unit  equals  0.1  c.c.)  and  the  amount  of  normal  salt  solution 
required  to  bring  the  total  volume  up  to  2.5  c.c.  after  the  addition 
of  the  amboceptor  and  corpuscles.  The  tubes  are  now  incubated 
for  one-half  hour  in  the  water-bath  at  37°  C,  after  which  the 
amboceptor  and   corpuscles  are  added. 

Tube  1  receives  0.5  c.c.  of  a  1  to  10,000  dilution  of  amboceptor 
serum  in  salt  solution  and  the  amount  is  increased  in  each  tube  until 
tube  15  contains  1  c.c.  of  a  1  to  1000  dilution  or  0.01  c.c.  of  pure 
serum.  The  eight  control  tubes  receive  the  various  reagents  as 
indicated  in  Table  I,  and  if  all  reagents  are  working  properly  the 
results  will  be  as  indicated. 

Table  I  also  indicates  the  results  of  the  titration  of  a  good  ambo- 
ceptor. It  will  be  seen  that  tubes  1  and  2  show  no  hemolysis, 
tubes  3,  4,  5,  6,  and  7  show  partial  hemolysis,  which  varies  from 
slight  to  almost  complete,  and  that  the  remainder  of  the  tubes  of 
the  titration  test  show  complete  hemolysis.  Tube  8,  containing 
0.3  c.c.  of  a  1  to  1000  dilution,  is  the  tube  which  contains  the  least 

1  Thompson:  Arch.  Int.  Med.,  1914,  xiii,  p.  904. 


COMPLEMENT-FIXATION   TESTS 


151 


amount  of  amboceptor  which  shows  complete  hemolysis,  and  there- 
fore 0.003  c.c.  is  the  unit. 

TABLE    I. — Titration  op  Amboceptor. 

Tube.  Serum.  Comp.        Ant.  NaCl.  Amboceptor.  Corp.  Total.  Results. 

1  0.1  0.1  0.1  1.2  0.5  of  1  to  10,000  0.5  2.5  NH 

2  0.1  0.1  0.1  1.1  0.6  of  1  to  10,000  0.5  2.5  NH 

3  0.1  0.1  0.1  1.0  0.7  of  1  to  10.000  0.5  2.5  PH 

4  0.1  0.1  0.1  0.9  0.8  of  1  to  10,000  0.5  2.5  PH 

5  0.1  0.1  0.1  0.8  0.9  of  1  to  10,000  0.5  2.5  PH 

6  0.1  0.1  0.1  1.6  0.1  of  1  to     1,000  0.5  2.5  PH 

7  0.1  0.1  0.1  1.5  0.2  of  1  to     1,000  0.5  2.5  PH 

8  0.1  0.1  0.1  1.4  0.3  of  1  to     1,000  0.5  2.5  H 

9  0.1  0.1  0.1  1.3  0.4oflto     1,000  0.5  2.5  H 

10  0.1  0.1  0.1  1.2  0.5oflto     1,000  0.5  2.5  H 

11  0.1  0.1  0.1  1.1  0.6oflto    1,000  0.6  2.5  H 

12  0.1  0.1  0.1  1.0  0.7  of  1  to     1,000  0.5  2.5  H 

13  0.1  0.1  0.1  0.9  0.8  of  1  to    1.000  0.5  2.5  H 

14  0.1  0.1  0.1  0.8  0.9  of  1  to     1,000  0.5  2.5  H 

15  0.1  0.1  0.1  0.7  l.Ooflto     1,000  0.5  2.5  H 

16  0.0  0.1  0.0  0.9  l.Ooflto     1,000  0.5  2.5  H 

17  0.0  0.1  0.1  0.8  l.Ooflto     1,000  0.5  2.5  H 

18  0.0  0.1  0.1  1.8         0.5  2.5  NH 

19  0.0  0.1  0.0  1.9          0.5  2.5  NH 

20  0.0  0.0  0.1  0.9  l.Ooflto     1,000  0.5  2.5  NH 

21  0.0  0.0  0.1  1.9          0.5  2.5  NH 

22  0.0  0.0  0.0  1.0  l.Ooflto     1,000  0.5  2.5  NH 

23  0.0  0.0  0.0  2.0         0.5  2.5  NH 


In  the  actual  'performance  of  the  test  1  unit  and  only  1  unit  is  employed. 
It  has  been  objected  that  sera  vary  in  their  anticomplementary 
effect,  and  that  a  false  positive  may  result  from  using  an  amount  of 
amboceptor,  which,  while  it  will  completely  hemolyze  the  corpuscles 
when  used  with  the  titration  serum,  will  not  do  so  with  all  the  nega- 
tive sera  tested,  owing  to  a  greater  amount  of  anticomplementary 
substances  in  the  latter.  That  sera  do  vary  in  their  anticomple- 
mentary effect  is  undoubtedly  true,  but  it  is  hard  to  believe  that 
any  serum  to  be  tested  will  contain  more  anticomplementary  sub- 
stance than  the  pooled  sera  of  several  known  non-luetic  individuals. 
In  fact,  this  has  been  found  to  be  true  in  practice,  especially  when 
the  pooled  sera  are  obtained,  as  in  the  author's  laboratory.  Here 
the  practice  is  to  preserve  all  negative  sera  and  just  before  titrating 
to  pool  a  sufficient  quantity  of  those  sera  remaining  uncontaminated 
and  inactive.  This  inactivation  destroys  to  a  large  extent  the 
anticomplementary  substances.  If  there  is  any  discrepancy  between 
the  anticomplementary  substances  contained  in  the  titrating  sera 
and  the  sera  to  be  tested,  there  certainly  would  be  more  of  such 
substances  in  the  titrating  sera,  as  the  sera  to  be  tested  are  usually 
fresh. 

Owing  to  the  fact  that  a  good  amboceptor  varies  little  if  any  in  its 
titer  over  periods  as  long  as  several  months,  it  has  been  found  more 


152 


LABORATORY  DIAGNOSIS 


convenient  when  "salted"  complement  is  used  to  fix  the  amboceptor 
unit  and  titrate  the  complement  before  each  series  of  tests.  If,  for 
example,  the  amboceptor  unit  with  0.1  c.c.  of  pure  guinea-pig 
serum  as  complement  has  been  found  to  be  0.3  c.c.  of  a  1  to  1000 
dilution  or  0.003  c.c,  a  slightly  greater  quantity,  that  is,  0.4  c.c. 
of  a  1  to  1000  dilution,  is  used  as  the  unit,  and  complement  is  added 
to  each  tube  in  increasing  amounts,  asjndicated  in  Table  II.  The 
control  tubes  and  the  results  of  an  average  titration  also  are 
indicated. 

TABLE    II. — Titration  of  Complement. 

Tube.  Serum.  Comp.  Ant.  NaCl.  Amboceptor.  Corp.  Total.  Results. 

1  0.1  0.5  0.1  0.8  0.4  of  1  to  1000  0.5  2.5  PH 

2  0.1  0.6  0.1  0.9  0.4  of  1  to  1000  0.5  2.5  PH 

3  0.1  0.7  0.1  0.7           0.4 0.5  2.5  PH 

4  0.1  0.8  0.1  0.6           0.4 0.5  2.5  H 

5  0.1  0.9  0.1  0.5           0.4 0.5  2.5  H 

6  0.1  1.0  0.1  0.4           0.4 0.5  2.5  H 

7  0.0  1.0  0.0  0.6  0.4 0.5  2.5  H 

8  0.0  1.0  0.1  0.5           0.4 0.5  2.5  H 

9  0.0  1.0  0.1  0.9           0.0 0.5  2.5  NH 

10  0.0  1.0  0.0  1.0  0.0 0.5  2.5  NH 

11  0.0  0.0  0.1  1.5  0.4 0.5  2.5  NH 

12  0.0  0.0  0.1  1.9  0.0 0.5  2.5  NH 

13  0.0  0.0  0.0  1.6  0.4 0.5  2.5  NH 

14  0.0  0.0  0.0  2.0  0.0 0.5  2.5  NH. 

The  Author's  Method  of  Titrating  Antigen. — The  first  and  most 
important  factor  to  be  considered  in  the  titration  of  antigen  is  its 
hemolytic  effect,  and  no  antigen  should  be  used,  which,  of  itself, 
in  an  amount  considerably  in  excess  of  the  antigenic  unit,  will 
cause  hemolysis.  This  is  determined  by  adding  to  the  corpuscle 
suspension  increasing  amounts  of  antigen,  as  indicated  in  Table  III, 
and  the  tubes  incubated  for  one  hour. 

TABLE   III. — Titration  of  Antigen.     (Hemolytic  Effect.) 


Tube. 

Ant. 

Corp. 

NaCl. 

Total. 

Results. 

1 

0.5  of  1  to  100 

0.5 

1.5 

2.5 

NH 

2 

0.6  of  1  to  100 

0.5 

1.4 

2.5 

NH 

3 

0.7  of  1  to  100 

0.5 

1.3 

2.5 

NH 

4 

0.8  of  1  to  100 

0.5 

1.2 

2.5 

NH 

5 

0 . 9  of  1  to  100 

0.5 

1.1 

2.5 

NH 

6 

0.1  of  1  to 

10 

0.5 

1.9 

2.5 

NH 

7 

0.2  of  1  to 

10 

0.5 

1.8 

2.5 

NH 

8 

0 . 3  of  1  to 

10 

0.5 

1.7 

2.5 

NH 

9 

0.4  of  1  to 

10 

0.5 

1.6 

2.5 

NH 

10 

0.5  of  1  to 

10 

0.5 

1.5 

2.5 

NH 

11 

0 . 6  of  1  to 

10 

0.5 

1.4 

2.5 

NH 

12 

0 . 7  of  1  to 

10 

0.5 

1.3 

2.5 

NH 

13 

0 . 8  of  1  to 

10 

0.5 

1.3 

2.5 

NH 

14 

0.9  of  1  to 

10 

0.5 

1.1 

2.5 

NH 

15 

1 . 0  of  1  to 

10 

0.5 

1.0 

2.5 

NH 

16 

1 . 5  of  1  to 

10 

0.5 

0.5 

2.5 

PH 

17 

2.0  of  1  to 

10 

0.5 

0.0 

2.5 

H 

COMPLEMENT-FIXATION   TESTS  153 

A  good  antigen  will  show  no  hemolysis  in  amounts  up  to  1  c.c. 
of  a  1  to  10  dilution. 

The  second  point  to  be  determined  is  the  anticomplementary 
effect  of  the  antigen.  In  a  good  antigen  this  effect  must  not  be 
evident  in  an  amount  considerably  greater  than  the  antigenic  unit. 
A  series  of  eight  tubes  is  arranged,  as  in  Table  IV;  0.1  c.c.  of  a  known 
negative,  inactivated  serum  is  placed  in  each  tube;  0.1  c.c.  of 
complement,  increasing  amounts  of  antigen,  and  enough  salt  solu- 
tion to  bring  the  total  volume,  when  amboceptor  and  corpuscles 
are  added,  to  2.5  c.c.  The  tubes  are  now  incubated  thirty  minutes 
in  the  water-bath  at  37°  C,  after  which  1  unit  of  previously  titrated 
amboceptor  and  0.5  c.c.  of  corpuscle  suspension  are  added,  and  the 
incubation  continued  one  hour.  The  tube  which  contains  the  largest 
amount  of  antigen  in  which  hemolysis  is  complete  is  recorded. 


TABLE    IV.- 

—Titration  of  Ant 

IGEN.       ( 

Anticoii 

iplemeni 

tary  Eff 

ect.) 

Tube. 

Serum. 

Comp. 

Ant. 

NaCl. 

Amb. 

Corp. 

Total. 

Results. 

1 

0.1 

0.1 

0.6  of  1  to  100 

1.1 

0.1 

0.5 

2.5 

H 

2 

0.1 

0.1 

0 . 8  of  1  to  100 

0.9 

0.1 

0.5 

2.5 

H 

3 

0.1 

0.1 

1.0  of  1  to  100 

0.7 

0.1 

0.5 

2.5 

H 

4 

0.1 

0.1 

1.2  of  1  to  100 

0.5 

0.1 

0.5 

2.5 

H 

5 

0.1 

0.1 

1.4  of  1  to  100 

0.3 

0.1 

0.5 

2.5 

H 

6 

0.1 

0.1 

1 . 6  of  1  to  100 

0.1 

0.1 

0.5 

2.5 

H 

7 

0.1 

0.1 

0 . 9  of  1  to    50 

0.8 

0.1 

0.5 

2.5 

PH 

8 

0.1 

0.1 

0 . 2  of  1  to    10 

1.5 

0.1 

0.5 

2.5 

PH 

The  next  and  final  point  in  the  titration  of  antigen  is  the  deter- 
mination of  the  antigenic  unit.  This  titration  is  identical  with  the 
determination  of  the  anticomplementary  effect,  except  that  instead  of 
using  a  known  negative  serum,  a  known  positive  serum  is  employed. 
In  fact,  these  two  titrations  may  be,  and  usually  are,  carried  out  at 
one  time.  After  the  final  incubation  the  tube  is  determined  which 
contains  the  smallest  amount  of  antigen  in  which  inhibition  of 
hemolysis  is  complete. 


TABLE   v.— Titration  of 

Antigen. 

(Antig< 

enic  Unit.) 

Tube. 

Serum. 

Comp. 

Ant. 

NaCl. 

Amb. 

Corp. 

Total. 

Results. 

1 

0.1 

0.1 

0.6  of  1  to  100 

1.1 

0.1 

0.5 

2.5 

PH 

2 

0.1 

0.1 

0.8  of  1  to  100 

0.9 

0.1 

0.5 

2.5 

NH 

3 

0.1 

0.1 

1.0  of  1  to  100 

0.7 

0.1 

0.5 

2.5 

NH 

4 

0.1 

0.1 

1 . 2  of  1  to  100 

0.5 

0.1 

0.5 

2.5 

NH 

5 

0.1 

0.1 

1.4  of  1  to  100 

0.3 

0.1 

0.5 

2.5 

NH 

6 

0.1 

0.1 

1.6  of  1  to  100 

0.1 

0.1 

0.5 

2.5 

NH 

7 

0.1 

0.1 

0.9  of  1  to    50 

0.8 

0.1 

0.5 

2.5 

NH 

8 

0.1 

0.1 

0.2  of  1  to    10 

1.5 

0.1 

0.5 

2.5 

NH 

The  antigenic  unit  is  that  amount  of  antigen  which  is  the  average 
of  the  smallest  amount  which  will  completely  inhibit  hemolysis  with 
a  known  positive  serum,  and  the  largest  amount  w^hich  will  cause 


154  LABORATORY  DIAGNOSIS 

no  inhibition  with  a  known  negative  serum.  For  example,  if  it 
has  been  found  that  0.8  c.c.  of  a  1  to  100  dilution  completely  inhibits 
hemolysis  with  a  known  positive  serum,  and  1.6  c.c.  of  a  1  to  100 
dilution  is  the  largest  amount  which  does  not  inhibit  hemolysis  with 
a  known  negative  serum,  1.2  c.c.  of  a  1  :  1000  dilution,  or,  for  practical 
purposes,  0.1  c.e.  of  a  1  to  10  dilution  is  the  antigenic  unit. 

Performance  of  Test. — In  the  actual  performance  of  the  test  a 
tube  rack  with  two  parallel  rows  of  holes  is  used.  Two  tubes  are 
required  for  each  serum,  as  well  as  two  tubes  each  for  positive  and 
negative  control  sera.  Into  the  rear  tube  for  each  serum  is 
placed  0.1  c.c.  of  the  serum,  1  unit  of  complement,  and  a  sufficient 
quantity  of  salt  solution  to  bring  the  total  volume  in  each  tube  up 
to  2.5  c.c.  when  amboceptor  and  corpuscles  are  added.  Into  the 
front  tubes  are  placed  like  amounts  of  serum,  complement  and  salt 
solution  and  0.1  c.c.  of  antigen  (so  diluted  that  0.1  c.c.  equals  1 
unit).  The  tubes  are  now  incubated  thirty  minutes  in  the  water- 
bath  at  37°  C,  after  which  0.4  c.c.  of  amboceptor,  or  0.1  c.c.  (so 
diluted  that  0.1  c.c.  equals  1  unit)  and  0.5  c.c.  of  corpuscle  suspension 
are  added.  Following  this,  incubation  is  continued  one  hour,  after 
which  the  tubes  are  removed  to  a  cool  place  and  permitted  to  stand 
two  or  three  hours,  when  the  results  are  read. 

Complete  hemolysis  of  the  corpuscles  in  the  front  tube  is  negative 
and  is  recorded  — .  Complete  inhibition  of  hemolysis  in  the  front 
tube  is  strongly  positive  and  is  designated  +  +  +  +  •  Varying 
degrees  of  inhibition  are  indicated  differently,  such  as  25  per  cent.  +  , 
50  per  cent.  ++,  and  75  per  cent.  +  +  +  .  The  estimating  of 
inhibition  must,  in  the  nature  of  things,  depend  largely  upon  the 
personal  factor,  and  different  workers  read  the  results  differently. 

Theory  of  Complement-fixation  in  Syphilis. — As  stated  above, 
since  the  discovery  that  positive  complement-fixation  reactions 
may  be  obtained  in  syphilis  with  antigens  prepared  from  extracts 
of  normaf  organs  it  has  been  known  that  this  phenomenon  is  not 
wholly,  at  least,  a  true  antigen-antibody  reaction. 

However,  since  positive  reactions  are  obtained  with  some  syphi- 
litic sera  and  negative  reactions  with  all  non-syphilitic  sera,  when 
treponemata  culture  antigens  are  used,  it  is  probable  that  true 
syphilitic  antibodies  are  produced.  Nevertheless,  as  pointed  out 
above,  other  extracts  are  much  more  reliable  and  therefore  the  sera 
of  syphilitics  must  contain  some  substance  which  resembles  anti- 
bodies, and  which  in  the  presence  of  complement  has  a  special 
affinity  for  lipoidal  substances.  The  nature  of  this  substance  is 
still  in  doubt.  It  is  surely  developed  in  the  body  by  the  presence, 
and  probably  by  the  activity,  of  the  Treponema  pallidum,  and  it 
may  be  a  true  antibody  acting  in  a  deleterious  manner  on  the 
invading  organism. 


PLATE  11 


++++       +++ 


++ 


End-results  of  Wassermann  Reaction,  showing  Varying 
Reactions    from   +  +  +  +  to  — . 


COMPLEMENT-FIXATION  TESTS  155 

The  author's  antigen  is  prepared  from  lipoidal  extracts  and 
Treponema  pallidum  extracts  so  that  it  will  react  with  the  lipoido- 
trophic  or  antibody-like  substance  present  in  luetic  sera  as  well  as 
with  any  true  Treponema  pallidum  antibodies  which  may  be  present. 

Value  of  Complement-fixation  Tests  in  Syphilis. — The  Wasser- 
mann  reaction  and  its  modifications  have  developed  into  one  of 
the  most  useful  of  laboratory  tests,  yet  in  the  hands  of  the  inex- 
perienced they  may  lead  to  most  disastrous  resuHs.  Not  only  may 
a  negative  be  recorded  when  it  should  have  been  positive  and  the 
patient  go  his  way  infecting  others  in  the  thought  that  he  is  free 
from  taint,  but  a  false  positive  may  be  registered  for  an  uninfected 
one,  and  the  stigma  of  thinking  he  has  syphilis  be  carried  through 
life.  But  in  the  hands  of  one  skilled  in  serology  and  understanding 
the  factors  for  error  and  the  limitations  of  the  test  its  value  is 
inestimable. 

The  author  does  not  consider  the  complement-fixation  test  for 
syphilis  as  the  suiimm  honum  in  the  diagnosis  of  this  disease.  It  is 
but  one  sjinptom,  but  one  link  in  the  chain  of  evidence,  and  must 
be  interpreted  in  the  light  of  the  history  and  clinical  findings. 

A  weakly  positive  Wassermann  test  in  the  absence  of  history  or 
clinical  evidence  of  syphilis  should  never  be  taken  as  final.  And 
even  a  strongly  positive  test  in  such  a  case  should  be  repeated  and 
sent  to  another  serologist  for  corroboration. 

One  negative  test  should  not  be  taken  as  disproving  the  presence 
of  syphilis,  especially  in  cases  with  suspicious  history  or  clinical 
evidences  of  the  disease,  as  it  has  been  shown  that  the  reaction 
may  vary  from  day  to  day  in  untreated  syphilitics.^  However, 
several  negative  tests,  including  the  so-called  provocative  Wasser- 
mann, performed  at  considerable  intervals,  should  be  accepted  as 
evidence  of  the  absence  of  syphilis,  save  in  the  presence  of  unmis- 
takable clinical  sjTuptoms.  This  latter  condition  is  extremely  rare, 
except  during  the  early  course  of  the  disease  when  the  lesions  are 
limited  to  the  chancre,  at  which  time  Craig^  has  shown,  as  would 
be  expected,  the  percentage  of  positives  varies  from  27.6  in  the 
first  week  to  79.4  in  the  fifth  week. 

In  regard  to  the  percentage  of  positive  Wassermaim  reactions 
obtained  during  the  later  course  of  the  disease  investigators  differ. 
The  consensus  of  opinion,  however,  seems  to  be  that  in  untreated 
cases  practically  100  per  cent,  of  s\T)hilitics  will  give  a  positive 
Wassermann  during  the  first  year.  Treatment  during  this  period 
of  the  disease  has  a  marked  effect  upon  the  Wassermann  reaction, 
and  if  sufficiently  intensive  and  carried  out  over  a  considerable 
length  of  time  will  usually  cause  a  positive  test  to  become  negative. 

1  Craig:  Jour.  Am.  Med.  Assn.,  1914,  Ixii,  p.  1232. 

2  Studies  in  Syphilis,  War  Department  Bulletin  No.  3,  Washington,  1913,  p.  37. 


156  LABORATORY  DIAGNOSIS 

There  are  some  cases,  however,  which  resist  all  treatment,  the 
Wassermann  always  remaining  positive. 

It  is  in  the  later  course  of  syphilis,  especially  when  lesions  of  the 
viscera  develop,  that  the  Wassermann  reaction  has  its  greatest 
value.  In  untreated  cases  of  this  nature  the  test  is  positive  in 
about  95  per  cent,  of  the  cases.  Treatment  in  these  conditions 
also  will  markedly  influence  the  reaction. 

In  syphilis  of  the  nervous  system,  especially  in  tabes  and  paresis, 
the  Wassermann  reaction  of  the  blood  is  quite  constantly  positive. 

In  paresis  it  varies  from  90.9  per  cent.  (Kaplan^)  to  100  per  cent. 
(Nonne^).  While  in  tabes  the  reaction  is  positive  in  about  70 
per  cent,  of  the  cases.  In  syphilitic  involvement  of  the  central 
nervous  system  other  than  tabes  and  paresis  the  blood  serum  reacts 
positively  in  from  75  to  80  per  cent,  of  the  cases. 

In  congenital  syphilis,  according  to  Holt, ^  practically  100  per  cent, 
of  cases  show  a  positive  Wassermann  even  if  treated  with  mercury, 
unless  the  treatment  has  been  most  vigorous  and  protracted. 

"One  other  very  important  factor  which  influences  the  Wassermann 
reaction  has  been  pointed  out  by  Craig  and  Nichols.^  These 
investigators  have  shown  that  the  ingestion  of  considerable  quan- 
tities of  alcohol  by  the  patient  within  twenty-four  hours  of  taking 
his  blood,  and  in  some  cases  as  long  as  three  days,  may  change  a  posi- 
tive into  a  negative  reaction.  This  observation  the  writer  has 
confirmed  in  a  number  of  instances. 

That  two  or  more  serologists  may  differ  materially,  or  even  have 
contradictory  findings,  on  the  same  sera  has  been  shown  by  Wol- 
barst.^  In  85  cases  specimens  of  blood  collected  in  three  test-tubes 
at  the  same  time  were  sent  to  three  different  well-known  serologists 
for  examination.  Of  the  85  cases  the  serologists  obtained  the  same 
results  in  36  cases,  slightly  different  results  in  16  cases,  and  abso- 
lutely contradictory  findings  were  reported  in  33  cases. 

The  obvious  reason  for  these  discrepancies  is  to  be  found  in  the 
differences  in  technic  employed  by  the  three  serologists,  and  the 
obvious  remedy  is  to  standardize  the  complement-fixation  test  for 
syphilis,  and  to  have  the  reagents  prepared  on  a  large  scale  in  a  central 
laboratory  to  he  distributed  to  the  various  serologists.  And,  finally, 
it  should  be  reiterated  that  this  reaction  should  be  interpreted  only  in 
the  light  of  clinical  evidence. 

Extensive  as  is  the  value  of  the  complement-fixation  test  in  the 
diagnosis  of  syphilis  it  is  in  the  control  of  the  treatment  that  its 

1  Serology  of  Nervous  and  Mental  Diseases,  Philadelphia  and  London,  1914,  p. 
191. 

2  Syphilis  and  the  Nervous  System,  Philadelphia  and  London,  1913,  p.  352. 

3  Am.  Jour.  Dis.  Child.,  1913,  vi,  p.  166. 
^  Jour.  Am.  Med.  Assn.,  1911,  Ivii,  p.  474. 

6  Interstate  Med.  Jour.,  1915,  xxii,  p.  109. 


COMPLEMENT-FIXATION  TESTS  157 

greatest  value  is  observed.     This  phase  of  the  test  will  be  discussed 
fully  in  the  chapter  on  Treatment. 

Provocative  Wassermann  Test. — It  has  been  observed  that  in 
certain  individuals  who  give  a  negative  complement-fixation  test 
for  syphilis  this  negative  may  be  converted  into  a  positive  by  the 
injection  of  a  dose  of  salvarsan,  or  by  the  administration  of  mercury, 
either  internally  or  by  inunction,  for  a  period  of  ten  days  to  two 
weeks.  The  explanation  of  this  phenomenon  is  that  by  killing  the 
treponemata  present  in  the  body  and  the  consequent  liberation  of 
endotoxins,  the  substances  concerned  in  the  binding  of  complement 
with  antigen  are  stimulated  to  greater  production.  Or  it  may  be 
that  the  drug  administered  is  insufficient  to  kill  the  organisms  but 
stimulates  them  to  greater  activity.  If  we  are  to  believe,  as  we 
have  good  grounds  for  doing,  that  a  positive  Wassermann  denotes 
the  presence  of  living  treponemata,  the  latter  explanation  is  the 
more  plausible. 

The  usual  method  of  procedure  is  to  administer  0.2-0.4  gram  of 
salvarsan  intravenously,  taking  the  blood  for  examination  at  the 
same  time,  and  to  test  it  on  several  succeeding  days.  It  has  been 
found  that  it  is  most  likely  to  become  positive  on  the  first  or  second 
day  following,  but  it  may  remain  negative  for  as  long  as  two  weeks, 
finally  becoming  positive.  It  is  the  custom  of  the  author  to  collect 
the  blood  for  examination  twenty-four  and  forty-eight  hours  after 
administration  of  the  salvarsan,  and  if  negative,  to  test  it  again 
after  one  week  and  finally  after  two  weeks. 

Wassermann  Reaction  in  Diseases  other  than  Syphilis. — Some 
diseases  other  than  syphilis  will  occasionally  give  a  positive 
Wassermann  reaction. 

In  framhesia  (yaws)  in  which  the  infecting  organism,  the 
Treponema  pertenue  is  similar  to  the  Treponema  pallidum,  a 
positive  Wassermann  has  been  reported. 

Leprosy  of  the  tuberous  type  also  has  been  shown  to  give  positive 
results,^  although  in  two  cases  of  leprosy  of  this  type  recently  seen 
by  the  author  the  Wassermann  was  negative.  Malaria  during  the 
febrile  stage  when  plasmodioB  are  present  will  often  cause  a  positive 
reaction.  The  author  has  had  occasion  to  observe  several  such 
cases.  One  in  particular  is  striking.  Upon  performing  the  Wasser- 
mann with  the  blood  of  this  patient  a  4  plus  reaction  was  observed. 
Subsequent  to  taking  the  blood  for  the  Wassermann  it  was  dis- 
covered that  the  patient  had  a  temperature  of  101°  F.,  and  a  smear 
of  the  blood  revealed  many  plasmodise  of  the  estivo-autumnal 
type.  He  was  thoroughly  cinchonized,  and  one  week  later  his 
blood  was  absolutely  negative  to  both  the  complement-fixation  test 
and  to  malaria]  parasites. 

1  Fox:  Am.  Jour.  Med.  Sc,  1910,  cxxxix,  p.  725. 


158  LABORATORY  DIAGNOSIS 

In  pellagra,  Bass^  and  Fox^  each  secured  faintly  positive  Wasser- 
mann  reactions  at  times.  The  author  in  35  cases  secured  no 
positive  findings. 

Richards^  and  later  Keyes^  pointed  out  that  a  condition  of  acidosis 
in  a  person  free  from  syphilis  will  make  his  blood  positive  to  the 
Wassermann  reaction. 

This  was  strikingly  illustrated  in  a  case  seen  by  the  author. 
This  patient,  a  Catholic  priest,  consulted  a  neurologist  near  Chicago 
for  a  chronic  headache  and  a  numbness  of  the  extremities.  A 
Wassermann  test  was  performed  which  was  positive,  and  anti- 
syphilitic  treatment  recommended.  Soon  after  this  the  patient 
came  to  Hot  Springs.  At  this  time  a  neurological  investigation 
revealed  that  the  lower  tendon  reflexes  were  markedly  diminished, 
the  left  knee-jerk  being  practically  abolished.  The  left  pupil  was 
slightly  larger  than  the  right,  although  both  reacted  to  light  and 
accommodation.  The  Wassermann  on  the  blood  being  found 
negative  and  the  urine  showing  sugar,  a  lumbar  puncture  was 
suggested.  This  was  consented  to  and  the  spinal  fluid  showed  a 
negative  Wassermann,  no  increase  in  globulin  and  only  7  lympho- 
cytes per  cubic  millimeter.  Diabetic  treatment  caused  the  dis- 
appearance of  the  sugar  from  the  urine  and  a  marked  improvement 
in  the  general  condition. 

It  will  be  seen  from  the  above  that  all  of  the  diseases  other  than 
syphilis,  with  the  possible  exception  of  yaws,  which  react  positively 
to  the  Wassermann  test  can  usually  readily  be  excluded.  It  is 
possible,  however,  for  a  patient  to  be  suffering  with  syphilis  as 
well  as  one  of  the  above-mentioned  diseases. 

In  regard  to  a  positive  Wassermann  in  cases  of  acidosis,  Warthin 
and  Wilson^  recently  have  shown  that  of  six  diabetics  coming  to 
autopsy  all  six  showed  unmistakable  evidences  of  syphilis,  Tre- 
ponema pallida  being  found  in  four  of  them.  These  authors  state 
that  ''it  seems  very  probable,  therefore,  that  latent  syphilis  is  the 
chief  factor  in  the  production  of  the  form  of  pancreatitis  most 
frequently  associated  with  diabetes." 

The  Hecht-Weinberg  Reaction.^ — ^This  test,  which  depends  upon 
complement-fixation,  is  used  quite  extensively  by  some  serologists 
as  a  control  of  the  Wassermann.  The  natural  complement,  present 
in  all  human  sera,  and  the  natural  anti-sheep  amboceptor  present 
in  nearly  all  human  sera,  are  utilized,  which,  of  course,  makes  it 
essential  to  employ  only  fresh  sera. 

The  technic  followed  by  the  author  is  the  modification  of  Grad- 

1  New  York  Med.  Jour.,  1909,  xc,  p.  1000.  ^  ibid.,  p.  1206 

3  Jour.  Am.  Med.  Assn.,  1913,  Ix,  p.  1139.  "  Ibid.,  1915,  Ixiv,  p.  804. 

5  Am.  Jour.  Med.  Sc,  1916,  clii,  p.  157. 

6  Hecht:  Wien.  klin.  Wchnschr.,   1909,  xxii,  p.  265. 


OTHER  SEROLOGICAL   TESTS  159 

wohl/  and  consists  of  first  determining  tlie  so-called  hemolytic 
index  of  each  serum.  This  index  is  the  amount  of  natural  anti-sheep 
amboceptor  present,  and  is  determined  by  adding  varying  amounts 
of  sheep's  corpuscles  to  0.1  c.c.  of  the  serum  and  incubating-.  The 
actual  test  is  performed  by  combining  the  serum  and  antigen  (the 
acetone,  insoluble  lipoids  are  best)  in  increasing  quantities  and 
incubating  for  one-half  hour  to  fix  complement.  Following  this 
the  corpuscles  are  added  in  an  amount  depending  upon  the  hemo- 
lytic index,  and  the  incubation  continued  for  one-half  hour  when 
the  results  are  read;  complete  hemolysis  denoting  a  negative  and 
complete  inhibition  denoting  a  strong  positive. 

While  this  reaction  is  quite  sensitive  and  is  comparatively  simple, 
it  should  never  be  relied  upon  except  when  controlled  by  the 
Wassermann.  To  the  author's  mind  even  this  combination  is  not 
to  be  preferred  to  the  complement-fixation  test  as  performed  in  his 
laboratory. 

OTHER   SEROLOGICAL   TESTS, 

A  number  of  other  serological  tests  for  syphilis  depending  upon 
other  principles  than  the  phenomenon  of  complement-fixation  have 
been  devised. 

Cobra  Venom  Test  of  Weil.^ — This  test  depends  upon  the  fact  that 
the  natural  hemolyzing  effect  of  cobra  venom  on  human  corpuscles 
is  resisted  to  a  marked  degree  by  the  corpuscles  of  a  syphilitic.  It 
is  performed  by  adding  varying  dilutions  of  cobra  venom  to  the 
carefully  washed  corpuscles  of  the  patient  and  incubating.  Its 
simplicity  is  practically  the  only  feature  which  recommends  this 
test,  as  it  is  not  as  sensitive  as  the  Wassermann  reaction,  especially 
with  the  newer  titration  technic  and  antigens,  and  occasionally  a 
positive  is  found  in  cancer.  In  the  differentiation  of  tuberculosis 
and  syphilis  of  the  lungs  this  test  may  be  of  value,  as  in  the  former 
disease  the  red  cells  are  hypersensitive  to  the  cobra  venom. 

Precipitin  Tests. — A  number  of  workers  have  attempted  to 
diagnose  syphilis  by  the  use  of  precipitin  tests,  and  while  with  some 
methods  of  technic  a  certain  percentage  of  positive  results  may  be 
obtained  in  syphilitic  individuals,  a  large  number  of  non-syphilitics 
will  also  be  positive. 

Olitsky  and  Olmstead,'  after  citing  the  work  of  a  large  number 
of  investigators  in  this  field  and  giving  the  results  of  their  own  tests, 
reach  the  conclusion  that  the  Wassermann  reaction  is  by  far  more 
reliable. 

1  Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  p.  240. 

2  Proc.  Soc.  Exper.  Biol,  and  Med.,  1909,  vi,  p.  49;  ibid.,  1909,  vii,  p.  2;  Jour, 
[nfect.  Dis.,  1909,  vi,  p.  688. 

3  Jour.  Am.  Med.  Assn.,  1914,  Ixii,  p.  293. 


160  LABORATORY  DIAGNOSIS 

Enzyme  Test. — The  principle  of  Abderhalden's  dialyzing  test  has 
been  applied  to  syphilis  but  as  yet  has  not  been  demonstrated  to 
be  of  practical  value.  The  method  of  procedure  usually  employed 
is  to  add  the  serum  of  a  patient  and  the  tissue  obtained  from  a 
human  condyloma  or  syphilitic  lesion  of  a  rabbit  testicle  prepared 
after  the  method  of  Abderhalden,  to  a  dialyzing  thimble,  place  in 
a  suitable  capsule  with  distilled  water,  cover  with  toluol  and 
incubate.  After  twelve  to  eighteen  hours  the  dialysate  is  tested 
with  ninhydrin  for  evidences  of  enzyme  action. 

Landau's  Color  Test.^ — The  reagent  for  this  test  as  first  reported 
consists  of  iodized  petrolatum  (0.025  c.c.  iodin  in  50  c.c.  white 
petrolatum),  but  was  later  changed  to  a  1  per  cent,  solution  of 
iodin  in  methanetetrachlorid.  To  0.2  c.c.  of  the  patient's  serum 
in  a  small  test-tube  is  added  0.01  c.c.  of  the  iodin  reagent.  The 
solutions  are  well  mixed  and  set  aside  for  four  hours  at  room 
temperature.  A  normal  serum  is  said  to  assume  a  whitish-gray 
appearance  and  is  opaque,  while  the  serum  of  a  syphilitic  is  a  clear 
transparent  yellow.  This  test  has  little  to  recommend  it,  as  it  has 
been  shown  to  sometimes  give  positive  results  with  non-luetic  sera 
and  negative  results  with  luetic  sera. 

LUETIN  REACTION. 

From  time  to  time  since  the  discovery  of  tuberculin  skin  reactions 
investigators^  have  attempted  to  apply  the  principle  to  the  diagnosis 
of  syphilis.  However,  to  Noguchi,^  belongs  the  honor  of  having 
developed  an  allergic  reaction  which  is  a  most  valuable  aid  in  the 
diagnosis  of  this  disease. 

Preparation. — ^The  material  used,  which  Noguchi  so  aptly  calls 
luetin,  is  prepared  from  pure  cultures  of  Treponema  pallidum  grown 
after  the  method  described  by  its  originator.  At  first  only  two 
strains  of  the  organisms  were  used,  but  later  six  strains  were 
employed. 

Tubes  of  the  treponemata  are  selected  which  have  grown  for 
six,  twelve,  twenty-four,  and  fifty  days,  and  which  show  good 
growths  of  the  organisms.  The  oil  is  poured  off,  the  tube  cut, 
the  agar  column  removed,  and  the  tissue  cut  off.  The  medium 
containing  the  cultures  is  carefully  ground  in  a  sterile  mortar  until 
a  thick  paste  results.  To  this  is  added  slowly  a  fluid  culture  of  the 
organisms  until  a  homogeneous  liquid  emulsion  is  secured.  This 
is  heated  for  one  hour  in  the  water-bath  at  60°  C,  and  0.5  per  cent. 

1  Wien.  klin.  Wchnschr.,  1913,  xxvi,  p.  1702. 

2  Kolmer:  Infection,  Immunity  and  Specific  Therapy,  Philadelphia  and  London, 
1915,  p.  601. 

3  Jour.  Exper.  Med.,  1911,  xiv,  p.  557;  Jour.  Am.  Med.  Assn..  1912,  Iviii,  p.  1163. 


LUETIN  REACTION  161 

tricresol  or  phenol  added  as  a  preservative.  Its  sterility  is  tested 
by  planting  on  suitable  culture  media  and  inoculating  rabbits 
intratesticularly. 

Experimentation. — At  first  the  new  preparation  was  tried  only  on 
rabbits.  These  animals  were  given  repeated  intravenous  injections 
of  pallidum  antigen  for  a  period  of  several  months  followed  by  a 
month's  rest.  After  which  the  luetin  was  injected  intradermally 
with  the  result  that  marked  inflammation  was  produced,  some 
even  showing  pustulation.  Normal  animals  injected  showed  no 
reaction. 

While  the  experiments  with  the  animals  were  still  being  carried 
on,  at  the  suggestion  of  Professor  Welch,  Noguchi  made  the  test 
on  human  beings.  Later,  luetin  was  distributed  by  its  originator 
to  a  large  number  of  physicians  both  in  Europe  and  America,  and 
before  long  it  was  placed  upon  the  market  by  a  number  of  manu- 
facturers of  biological  preparations. 

Mode  of  Application. — Luetin  is  injected  intradermally  by  means 
of  a  very  fine  sterile  needle  and  a  small  all-glass  syringe  graduated 
in  one-hundredths  of  a  cubic  centimeter.  Just  before  use  the 
material,  as  prepared  by  Noguchi,  is  diluted  one-half  with  sterile 
normal  salt  solution.^  The  dose  of  the  diluted  luetin  for  adults  is 
0.07  c.c,  while  children  are  given  0.05  c.c.  The  site  of  injection  is 
usually  the  upper  arm,  which  is  prepared  by  rubbing  with  alcohol. 
The  skin  is  drawn  taut  by  encircling  the  arm  from  the  inner  side 
with  the  thumb  and  middle  finger  of  the  left  hand.  The  injection 
is  made  with  the  right  hand,  the  bevel  of  the  needle  being  directed 
outward.  A  slightly  raised  white  papule  is  produced  if  the  point 
of  the  needle  is  within  the  skin  and  disappears  in  about  ten  minutes. 
If  the  needle  has  pierced  the  skin,  no  papule  results.  At  first 
Noguchi  recommended  a  control  injection  of  a  fluid  prepared  in 
exactly  the  same  manner  as  luetin  from  the  sterile  culture  media. 

Reaction. —  Negative. — Following  the  injection  of  luetin  into  the 
majority  of  normal  individuals  there  may  be  seen  after  twenty-four 
hours  a  small  erythematous  area  at  and  around  the  site  of  injection. 
This  reaction,  which  is  traumatic  in  nature,  produces  no  pain  or 
itching,  and  gradually  disappears  within  twenty-four  to  forty- 
eight  hours,  leaving  no  induration.  Occasionally  the  injection  will 
cause  the  formation  within  twenty-four  to  forty-eight  hours  of  a 
small  papule  which  commences  to  subside  within  seventy-two 
hours.  Following  even  this  kind  of  negative  reaction  no  induration 
is  left. 

Positive. — Pcipular  Form. — From  twenty-four  to  forty-eight  hours 
after  the  injection  a  red,  indurated,  raised  papule  of  5  to  10  mm. 

1  Some  of  the  commercial  luetin  is  injected  undiluted, 
11 


162  LABORATORY  DIAGNOSIS 

in  diameter  makes  its  appearance.  The  lesion  is  sometimes  sm*- 
rounded  by  an  erythematous  zone  which  may  be  slightly  edematous. 

Unlike  the  negative  papule,  it  gradually  progresses  for  forty -eight 
to  seventy-two  hours,  assuming  a  dark  bluish-red  color,  and  then 
slowly  subsiding,  entirely  disappearing  within  a  week  or  ten  days. 
A  slight  induration  may  be  left  for  a  longer  period. 

This  type  of  reaction  is  most  frequently  observed  during  the 
first  year  of  the  disease  in  individuals  who  have  had  some  mercurial 
treatment  and  who  show  no  clinical  evidences  of  syphilis.  It  is 
also  frequently  observed  in  hereditary  lues,  especially  during  the 
first  year. 

Pustidar  Form. — In  the  beginning  this  type  of  reaction  assumes 
the  papillary  form,  which  lasts  four  or  five  days.  The  surface  of 
the  indurated  papule  then  shows  a  number  of  small  vesicles  and 
the  centre  will  be  observed  to  have  become  slightly  soft.  After  this 
the  lesion  becomes  a  definite  pustule,  at  first  filled  with  a  slightly 
opaque  serum,  which  later  develops  into  true  pus.  At  this  stage 
there  are  more  or  less  pain  and  itching.  The  pustule  soon  ruptures 
either  spontaneously  or  by  contact  with  the  clothing,  leaving  an 
open  sore  surrounded  by  an  indurated  margin.  Following  the 
evacuation  of  the  pus  the  cavity  is  covered  by  a  thin  scab,  which 
falls  off  in  the  course  of  a  few  days,  and  the  induration  gradually 
disappears,  leaving  little  or  no  scar.  However,  the  skin  remains 
pigmented  and  this  pigmentation  may  persist  for  several  months. 
Occasionally  this  form  of  lesion  does  not  break  down,  the  pus  being 
gradually  absorbed. 

The  pustular  type  of  reaction  is  seen  most  frequently  in  hereditary 
syphilis  of  long  standing,  and  in  the  acquired  form  in  the  later  years 
of  the  disease. 

Torpid  Form. — This  type  of  reaction  appears  to  be  negative  at 
first  and  then  after  a  period  varying  from  one  to  five  weeks  it  shows 
itself  positive  by  assuming  either  the  papular  or  pustular  form  and 
progressing  in  a  manner  as  described  for  those  lesions. 

The  torpid  or  delayed  form  of  reaction  may  occur  at  any  time 
in  the  course  of  the  disease  and  practically  always  when  the  patient 
is  under  treatment. 

Hemorrhagic  Form. — A  reaction  consisting  of  a  hemorrhagic 
exudate  has  been  described  as  occasionally  occurring.  In  this  type 
the  lesion  usually  breaks  spontaneously  and  is  of  about  the  same 
severity  and  duration  as  the  pustular  form  of  reaction. 

Kilgore^  has  reported  a  fifth  type  of  reaction  appearing  in  twenty- 
four  to  forty-eight  hours,  consisting  of  a  small,  slightly  indurated 
reddened  papule  surrounded  by  a  light  purplish  or  violet  areola 
of  35  to  40  mm.  in  diameter.    The  areola  is  seen  to  fade  in  the  next 

1  Jour.  Am.  Med.  Assn.,  1914,  Ixii,  p.  1236. 


PLATE  III 


Positive  Luetin   Reaction.     Pustular  Type. 


LUETIN  REACTION  163 

three  or  four  days  and  the  papule  to  increase  in  size  and  in  amount 
of  induration,  after  which  the  reaction  progresses  in  a  manner  similar 
to  the  ordinary  papular  form. 

Value  of  Luetin  Reaction. — Since  the  discovery  of  the  luetin  test 
in  1911  it  has  been  used  very  extensively  by  many  different  investi- 
gators and  its  value  established  beyond  dispute.  It  has  not  in  any 
sense  usurped  the  place  of  the  Wassermann  reaction,  but  merely 
acts  as  a  supplement  to  that  most  valuable  test.  While  the  Wasser- 
mann reaction  is  of  most  value  in  the  early  course  of  the  disease, 
especially  in  untreated  cases  (except  paresis)  the  luetin  test  is  of 
prime  value  in  the  latter  stages  when  clinical  evidence  is  lacking. 

Sherrick^  recently  has  thrown  some  doubt  on  the  specificity  of  the 
luetin  reaction.  This  writer  states  that  a  positive  luetin  reaction 
can  be  obtained  in  99  per  cent,  of  all  cases,  irrespective  of  the  pres- 
ence of  syphilis,  by  the  administration  of  potassium  iodide  or  other 
iodin-containing  drugs  either  simultaneously,  or  shortly  before  or 
after  the  injection  of  the  luetin.  He  also  points  out  that  other 
substances,  such  as  agar  and  starch,  injected  intradermally  will 
produce  reactions  similar  to  the  luetin  if  iodin  is  administered, 
but  with  these  substances  it  must  be  administered  within  a  shorter 
time  of  the  injection  than  is  the  case  with  the  luetin.  The  time  of 
administration  of  the  potassium  iodide  may  vary  greatly.  In 
one  case  giving  a  negative  luetin  test  the  drug  was  administered 
in  small  doses  two  months  later  which  was  immediately  followed 
by  a  positive  nodular  reaction.  On  discontinuing  the  iodide  the 
reaction  underwent  complete  involution,  but  returned  again  when 
the  drug  was  resumed  several  weeks  later. 

By  studying  the  observations  of  about  fifty  investigators  Noguchi^ 
has  presented  the  following  statistical  estimation  of  the  practical 
value  of  the  luetin  reaction  in  the  various  stages  of  syphilis  according 
to  the  classification  of  Ricord: 

Primary  Syphilis. — Positive  in  less  than  30  per  cent,  of  cases 
and. then  reaction  usually  very  mild. 

Secondary  Syphilis. — Positive  in  47  per  cent,  of  630  cases. 
Usually  mild  reactions. 

Tertiary  Syphilis. — Positive  in  about  80  per  cent,  of  cases. 
Very  severe  type  of  reaction,  usually  pustular. 

Congenital  Syphilis. — Positive  in  about  70  per  cent,  of  cases. 
One  observer  finding  93  per  cent,  of  75  cases  positive. 

Syphilis  of  the  Nervous  System. — Rarely  positive  in  acute  syphilitic 
meningitis,  but  positive  in  about  60  per  cent,  of  cases  of  paresis 
and  tabes. 

Visceral  Syphilis. — Positive  in  nearly  90  per  cent,  of  such  cases, 
especially  marked  in  aortic  insufficiency. 

1  Jour.  Am.  Mtd.  Assn.,  1915,  Ixv,  p.  404.    2  Ng-^y  York  Med.  Jour.,  1914,  c,  p.  34. 


164  LABORATORY  DIAGNOSIS 

CEREBROSPINAL   FLUID. 

Anatomy. — The  cerebrospinal  fluid  is  found  in  the  subarachnoid 
spaces  of  the  brain  and  spinal  cord.  These  spaces  are  formed  by 
the  inner  wall  of  the  subarachnoid  and  the  outer  wall  of  the  pia, 
and  there  is  direct  communication  between  the  fluid  of  the  brain 
and  that  of  the  spinal  cord.  The  fluid  in  the  ventricles  probably 
also  comes  in  contact  with  the  fluid  of  the  subarachnoid  spaces. 

Physiology. — The  cerebrospinal  fluid  was  for  a  long  time  considered 
to  be  an  ordinary  tissue  lymph  bathing  the  nervous  structures.  It 
is  now,  however,  almost  universally  regarded  as  mainly  a  true  secre- 
tory substance,  a  product  of  the  choroid  plexus,  and  it  has  also  been 
shown  that  the  injection  of  extract  of  this  plexus  will  cause  an 
increase  in  the  secretion  of  the  spinal  fluid.  The  normal  quantity 
of  fluid  secreted  is  an  unsettled  question.  It  has  been  demonstrated, 
however,  that  following  puncture  of  the  subarachnoid  space  a  con- 
tinuous flow  of  fluid  at  the  rate  of  100  c.c.  per  hour  or  more  may  be 
observed,  and  which  may  last  for  weeks. ^ 

The  functions  of  the  spinal  fluid  are:  (1)  it  protects  the  delicate 
structures  of  the  central  nervous  system  from  jar;  (2)  it  takes  up 
and  neutralizes  certain  substances  formed  by  the  metabolic  changes 
in  the  brain  and  from  them  forms  inert  organic  compounds  of  a 
complex  nature ;  (3)  according  to  Mott,^  by  the  presence  of  glucose 
in  the  spinal  fluid  it  seems  to  supply  the  nervous  system  with  energy; 
and  (4)  it  aids  in  keeping  up  the  physiological  equilibrium  of  volume 
during  dilatation  and  contraction  of  the  bloodvessels  and  in  certain 
pathological  conditions  such  as  the  development  of  tumors. 

The  absorption  of  the  cerebrospinal  fluid  seems  to  be  mainly,  at 
least,  through  the  venous  channels,  the  lymphatics  being  a  negli- 
gible factor. 

Physical  and  Chemical  Properties. — The  normal  cerebrospinal  fluid 
is  a  thin,  clear,  watery,  fluid  of  a  specific  gravity  of  1.003  to  1.008, 
and  an  alkaline  reaction.     It  is  odorless  and  tasteless. 

The  chemical  composition,  according  to  Karpas,^  is  as  follows: 
Water,  98.74  per  cent. 
Solids,  1.25  per  cent. 

Albumin  (in  form  of  globulin  and  albumose),  0.03  to  0.6 

per  cent. 
Dextrose,  0.4  to  1  per  cent. 
Potassium  salts,  phosphate  and  urea,  0.15  to  0.35  per  cent. 

The  number  of  cellular  elements  in  normal  cerebrospinal  fluid 

1  Kusonoki:  Virchows  Arch.  f.  path.  Anat.,  1914,  ccxv,  p.  184. 

2  Cited  by  Kaplan:  Serology  of  Nervous  and  Mental  Diseases,  Philadelphia  and 
London, 1914,  p.  19. 

8  Jour.  Am,  Med.  Assn.,  1913,  Ixi,  p.  262. 


CEREBROSPINAL  FLUID  165 

is  variously  stated  to  be  from  none  to  10  per  c.mm.  The  author 
has  never  seen  a  normal  individual  with  more  than  seven  lympho- 
cytes per  c.mm.  in  his  spinal  fluid,  and  regards  five  as  the  usual 
limit  for  normal  cell  counts.  In  fact,  it  is  probable  that  strictly 
normal  cerebrospinal  fluids  are  entirely  free  from  cellular  elements 
and  that  their  presence,  even  in  numbers  under  5  per  c.mm.,  denotes 
some  slight  irritation,  perhaps  transitory  in  character. 

Under  pathological  conditions  the  composition  of  the  cerebro- 
spinal fluid  may  vary  greatly.  This  is  especially  true  of  the  protein 
content  which  in  certain  conditions  is  markedly  increased.  The 
number  of  cells  present  also  may  be  greatly  raised.  It  has  been 
shown  that  while  the  potassium  content  of  the  fluid  may  vary  to  a 
considerable  extent  no  clinical  significance  can  be  attached  to  these 
variations.^ 

Rachicentesis. — Probably  the  first  person  to  perform  spinal  punc- 
ture was  Doctor  J.  Leonard  Corning,^  who,  in  1885,  demonstrated 
the  induction  of  analgesia  by  the  injection  of  cocain  into  the  sub- 
arachnoid space. 

It  was  not,  however,  until  1891  that  rachicentesis  was  performed 
for  the  purpose  of  withdrawing  spinal  fluid,  and  in  that  year  Quincke^ 
published  his  technic  for  this  procedure. 

Indications. — The  indications  for  spinal  puncture  are  mainly  for 
diagnosis,  although  therapeutically  this  procedure  is  of  value  for 
reducing  intracranial  pressure  and  for  the  intraspinal  administra- 
tion of  remedial  agents.  It  is  indicated  in  all  suspected  cases  of 
meningitis,  including  syphilis,  in  suspected  syphilitic  involvement 
of  the  brain  and  cord,  in  poliomyelitis,  and  in  tumors  of  the  cord. 

Contraindications. — Spinal  puncture  is  contraindicated  in  any 
markedly  weakened  physical  condition,  in  brain  tumors  of  the  pos- 
terior fossa,  except  in  the  most  urgent  cases,  when  a  very  small 
quantity  (not  over  1  or  2  c.c.)  may  be  withdrawn,  and  immediately 
replaced  with  sterile  normal  salt  solution,  in  marked  arteriosclerosis 
and  in  advanced  cardiac  affections. 

Technic. — The  author  has  found  the  most  convenient  position 
in  which  to  place  the  patient  for  lumbar  puncture  is  sitting,  although 
it  can  easily  be  performed  with  the  patient  in  bed,  in  which  case  he 
should  lie  on  his  right  side  near  the  edge  of  the  bed  and  be  instructed 
to  draw  his  knees  well  up  over  the  abdomen. 

If  the  sitting  posture  is  chosen,  the  patient  is  placed  in  a  chair 
sidewise  with  his  back  toward  the  operator  and  his  left  side  toward 
the  back  of  the  chair.    He  is  instructed  to  thrust  his  folded  hands 

1  Rosenbloom  and  Andrews:  Arch.  Int.  Med.,  1914,  xiv,  p.  536. 

2  Bush:  A  Reference  Handbook  of  the  Medical  Sciences,  New  York,  1900,  vii, 
p.  291. 

3  Berl.  klin.  Wchnschr.,  1891,  No.  38,  p.  929. 


166 


LABORATORY  DIAGNOSIS 


between  his  knees  and  "bow"  his  back.  The  hand  of  the  operator 
placed  under  the  patient's  abdomen  will  sometimes  assist  in  securing 
the  necessary  curve  to  the  spine. 

The  operator  now  places  the  index  finger  of  each  hand  on  the  pos- 
terosuperior  spines  of  the  ilii  and  with  the  thumb  of  the  left 
hand  searches  for  the  soft  spots  between  the  third  and  fourth 
and  the  fourth  and  fifth  lumbar  vertebrae. 

Having  by  this  preliminary  examination  determined  the  location 
of  the  soft  spots,  an  area  of  five  or  six  centimeters  around  them  is 
painted  with  iodin.  The  ventral  side  of  the  thumb  of  the  operator's 
left  hand  is  also  painted  with  iodin  and  the  exact  spot  for  the 
puncture  is  determined.    The  space  between  the  third  and  fourth 


Fig.  47. — Method  of  performing  spinal  puncture. 


vertebrae  is  usually  the  one  of  choice,  as  it  is  naturally  wider,  but 
occasionally  the  operator  finds  the  one  between  the  fourth  and  fifth 
better  adapted.  This  is  purely  a  matter  of  training.  As  a  rule  no 
anesthetic  is  necessary,  but  in  hysterical  or  nervous  individuals 
the  skin  may  be  infiltrated  with  a  2  per  cent,  novocain  solution  or 
anesthetized  with  ethylchloride. 

The  needle  should  be  slightly  flexible  and  provided  with  a  stilet. 
The  bore  may  vary  from  14-  to  20-guage.  The  author's  needle  is  of 
16-gauge  and  is  provided  with  an  outflow  tube  about  2  centimeters 
from  the  distal  end,  so  that  after  the  spinal  canal  is  pierced  and  a 
tube  held  under  this,  while  the  stilet  is  partially  withdrawn,  the 
fluid  will  flow  directly  into  the  tube  and  none  will  be  lost. 


CEREBROSPINAL  FLUID  167 

The  needle  is  inserted  with  a  steady  thrust  directly  in  the  median 
line  and  straight  in.  At  a  variable  distance  from  the  surface  the 
point  of  the  needle  will  meet  with  the  slight  resistance  of  the  mem- 
branes which,  wheri  overcome,  will  indicate  that  the  subarachnoid 
space  has  been  pierced. 


Fig.  48. — Author's  spinal  puncture  needle. 

It  is  advisable  to  collect  the  spinal  fluid  in  two  or  three  tubes, 
as  the  first  fluid  which  escapes,  even  with  the  most  careful  technic, 
may  contain  slight  amounts  of  blood.  Sometimes  the  entire  amount 
of  fluid  withdrawn  may  contain  blood  to  a  greater  or  less  extent, 
due  to  having  severed  a  small  vessel  in  making  the  puncture.  It  is 
needless  to  say  that  such  fluid  cannot  be  used  for  protein  determina- 
tions or  for  estimating  the  cellular  elements.  Slight  traces  of  blood, 
however,  do  not  interfere  with  the  Wassermann  reaction;  ()  or  8 
c.c.  are  usually  sufficient. 


Fig.  49 

It  occasionally  occurs  that  upon  withdrawing  the  stilet  from  the 
needle  no  fluid  escapes.  It  may  be  that  the  needle  is  inserted  too  far 
and  has  entered  the  anterior  wall  of  the  subarachnoid  space.  If  this 
is  the  case,  a  slight  withdrawal  of  the  needle  will  start  the  flow.  Or 
it  may  be  the  needle  is  not  inserted  far  enough,  when  upon  farther 
insertion  the  fluid  will  escape.  Finally,  the  bore  of  the  needle  may 
be  occluded  by  a  plug  of  fibrin  which  may  be  removed  by  replacing 
the  stilet  and  again  withdrawing  it. 

That  true   "dry  punctures"   do   occur  was   demonstrated   by 


168  LABORATORY  DIAGNOSIS 

Leszynsky/  who,  by  inserting  one  needle  between  the  third  and 
fourth  lumbar  vertebrae  and  another  between  the  fourth  and  fifth, 
injected  sterile  salt  solution  through  the  first  needle  and  observed 
its  escape  through  the  second  needle. 

Many  workers  estimate  the  pressure  of  the  fluid  by  attaching 
a  manometer  to  the  needle,  but  this  seems  to  the  author  a  useless 
procedure,  as  the  pressure  may  vary  greatly  in  normal  individuals 
and  is  not  constant  for  any  given  pathological  condition. 

After  obtaining  the  fluid  the  stilet  is  replaced,  the  needle  with- 
drawn and  a  drop  of  collodion  or  a  strip  of  adhesive  plaster  applied. 
The  patient  is  placed  in  bed  and  instructed  to  keep  his  head  low, 
preferably  without  a  pillow,  for  twenty-four  to  forty-eight  hours. 
It  is  also  desirable  to  place  the  patient  in  bed  for  twenty-four  hours 
before  the  operation. 

Untoward  Effects. — The  most  frequent  untoward  effect  of  spinal 
puncture  is  headache,  although  nausea  and  vomiting  may  occur. 
Sudden  death  may  follow  this  procedure  in  cases  of  cerebral  tumor. 
Paretics  and  tabetics  rarely  show  any  untoward  symptoms. 

The  headache  is  usually  controlled  by  the  administration  of 
asperin  or  some  other  mild  sedative  or  the  application  of  an  ice-bag. 
Bromides  and  potassium  iodide  have  also  been  recommended. 


METHODS   OF  EXAMINATION. 

Estimation  of  Protein. —  Nonne-A-pelt  Test. — This  test,  devised 
by  Nonne  and  Apelt,^  is  performed  as  follows:  1  c.c.  of  saturated 
solution  of  ammonium  sulphate  in  a  test-tube  is  heated  to  boiling 
and  then  permitted  to  cool.  To  this  is  now  added  1  c.c.  of  spinal 
fluid  by  overlaying  with  a  pipette.  If  the  globulin  is  increased  a 
more  or  less  distinct  gray  ring  will  occur  at  the  point  of  contact. 
The  tube  is  now  shaken  and  if  in  three  minutes  there  is  a  distinct 
cloudiness  the  reaction  is  positive. 

Noguchi  Butyric  Acid  Test.^ — To  0.2  c.c.  of  spinal  fluid  in  a 
test-tube  is  added  1  c.c.  of  a  10  per  cent,  solution  of  butyric  acid 
(Merck)  in  normal  salt  solution.  The  mixture  is  boiled  over  a 
Bunsen  flame  for  several  minutes,  after  which  0.1  c.c.  of  normal 
sodium  hydroxide  solution  is  quickly  added  and  the  boiling  continued 
for  a  few  seconds.  A  granular  or  flocculent  precipitate  will  indicate 
an  excess  of  globulin. 

1  Cited  by  Kaplan:  Serology  of  Nervous  and  Mental  Diseases,  Philadelphia  and 
London,    1913,    p.    21. 

2  Nonne:  Syphilis  and  the  Nervous  System,  Philadelphia  and  London,  1913, 
p.  341. 

*  Noguchi:  Serum  Diagnosis  of  Syphilis,  second  edition,  Philadelphia  and  London, 
1911,  p.  156. 


METHODS  OF  EXAMIXATIOX  169 

The  Author  s  Modification. — The  author  has  modified  the  Xoguchi 
technic  by  adding  the  sah  solution  and  but\Tic  acid  separately, 
as  follows:  To  0.2  c.c.  of  spinal  fluid  are  added  0.9  c.c.  of  normal 
salt  solution  and  0.1  c.c.  of  pure  but\Tic  acid.  The  remainder  of  the 
procedure  follows  the  Xoguchi  technic. 

Kaplan's  Methods — 0.5  c.c.  of  spinal  fluid  in  a  test-tube  are 
heated  until  boiling  occurs,  removed  from  the  flame  and  boiled 
again.  Three  drops  of  a  5  per  cent,  solution  of  butyric  acid  in  normal 
saline  are  added,  followed  quickly  by  underlying  0.5  c.c.  of  super- 
saturated ammonium  sulphate  solution  and  the  tube  set  aside  for 
twenty  minutes. 

An  excess  of  globulin  is  shown  as  a  "thick  granular,  pot-c-heese- 
like  ring."'  Normal  fluid  shows  no  ring.  A  rough  quantitative 
estimation  of  positive  fluids  is  made  by  using  five  tubes,  placing 
in  each,  respectively,  0.1, 0.2, 0.3, 0.4  and  0.5  c.c.  of  fluid  and  bringing 
the  total  in  each  up  to  0.5  c.c.  with  distilled  water,  then  proceeding 
as  above.  If  an  excess  of  globulin  is  observed  in  the  tube  containing 
0.1  c.c.  of  spinal  fluid,  the  reaction  is  termed  0.1  excess,  if  the  tube 
containing  0.2  c.c,  0.2  c.c.  excess,  and  so  on. 

Significance  of  Protein  Increase. — An  increase  in  the  protein  of 
the  spinal  fluid  indicates  an  organic  afi^ection  of  the  central  nervous 
system,  and  is  observed  in  practicaUy  all  s\-philitic  involvement  of 
these  organs.  It  will  not,  however,  distinguish  between  s\-phihtc 
and  non-s\'philitic  diseases,  nor  will  it  differentiate  the  various 
s^'philitic  processes. 

Lange  Collodidal  Gold  Test.- — ^AVhile  this  test  is  dependent  upon 
an  iacrease  in  the  protein  content  of  the  spinal  fluid,  it  does  not, 
however,  depend  upon  the  quantitative  increase,  as  the  strength 
of  the  reaction  bears  no  constant  relation  to  the  amount  of  protein 
present.  And  further,  it  is  impossible  in  our  present  state  of  knowl- 
edge to  account  for  aU  the  factors  concerned  in  the  phenomena  of 
the  reaction. 

Colloidal  gold  was  first  prepared  in  1857  by  ^Michael  Farada\'^ 
by  reducing  gold  chloride  with  phosphorus.  To  the  work  of 
Zsigmody,^  however,  we  are  indebted  for  the  preparation  of  clear 
solutions  or  suspensions  of  coUoidal  gold.  This  investigator  also 
demonstrated  that  the  red  color  of  the  solution  changes  to  a  blue 
with  the  precipitation  of  the  gold  as  an  extremely  fine  powder 
upon  the  addition  of  most  electroh-tes.  It  was  further  discovered 
that  solutions  of  protein  in  the  presence  of  an  electrohte  inhibited 
the  precipitate  (Goldschutz),  that  the  inhibitive  points  (Goldzahl) 

-  Kaplan:  Serologj-  of  Nervous  and  Mental  Diseases,  Philadelphia  and  London, 
1914,  p.  29. 

2  Lange:  Berl.  klin.  Wchnschr.,  1912,  xlix,  p.  S97. 

'  Proc.  Roy.  Soc,  18-57,  viii,  p.  -356. 

'Ann.  d.  Chem.  (Liebig'sj,  1898,  ecci,  p.  30. 


170  LABORATORY  DIAGNOSIS 

for  the  various  proteins  could  be  determined,  and  that  the  Goldzahl 
is  constant  for  each  protein. 

Lange,  with  these  facts  at  his  command,  was  able  to  demonstrate 
that  the  excessive  amounts  of  protein  found  in  the  spinal  fluid  under 
pathological  conditions  caused  the  precipitation  of  the  gold  solution, 
and  that  this  precipitation  occurred  within  definite  dilution  limits 
that  were  practically  specific  for  the  syphilitic  conditions  of  the 
central  nervous  system,  especially  paresis  and  taboparesis. 

Technic. — The  most  important  point  in  the  technic  is  absolute 
chemical  cleanliness.  All  glassware  should  be  boiled  in  ivory  soap- 
suds, thoroughly  rinsed  in  hot  running  water,  then  with  hydro- 
chloric acid  and  followed  by  plain  distilled  water  and  triple  distilled 
water.  Complete  sterility  of  glassware  is  not  necessary.  The 
spinal  fluid  must  be  fresh  when  tested  or  else  kept  absolutely  sterile. 
'Preparation  of  Reagent. — The  preparation  of  the  reagent  is  the 
most  difficult  point  of  the  technic  and  unless  the  instructions  are 
followed  absolutely  to  the  letter  failure  may  be  expected. 

Solutions  required: 

1.  Triply  distilled  water.  This  is  prepared  by  redistilling  freshly 
distilled  water  in  an  all-glass  still  without  rubber  connections. 

2.  Gold  chloride  solution.  (Merck)  (1  per  cent,  in  triply  dis- 
tilled water.) 

3.  Potassium  carbonate  solution.  (Merck's  Blue  Label)  (2  per 
cent,   in  triply  distilled   water.) 

4.  Formalin  solution.  (Merck's  40  per  cent.)  (1  per  cent,  in 
triply  distilled  water.) 

5.  Oxalic  acid  solution.  (Merck's  Blue  Label)  (1  per  cent,  in 
triply  distilled  water.) 

Li  a  Jena  glass  beaker  are  placed  500  c.c.  of  triply  distilled  water 
and  slowly  heated  over  a  large  Bunsen  burner  to  50°  C,  when  the 
temperature  is  quickly  raised  to  60°  C.  To  this  are  added  5  c.c. 
each  of  the  gold  chloride  solution  and  the  potassium  carbonate 
solution,  and  the  heating  continued  as  rapidly  as  possible.  At  80° 
C.  five  drops  of  the  oxalic  acid  solution  are  slowly  added  and  at 
90°  C.  the  flame  is  withdrawn  and  5  c.c.  of  the  formalin  solution 
are  added  drop  by  drop  while  stirring.  The  change  of  color  to 
a  clear  brilliant  red  with  a  slight  bluish  nuance  usually  is  gradual. 
It  may  occur  before  all  of  the  formaldehyde  is  added,  in  which  case 
it  should  be  stopped.  A  good  reagent  will  remain  unchanged  for 
months  if  placed  in  a  Jena  flask  and  kept  in  the  dark. 

Miller^  and  his  associates  recently  have  pointed  out  that  even 
beautifully  clear  solutions  sometimes  fail  to  respond  to  the  action 
of  paretic  spinal  fluids.     These  investigators  state  that  there  are 

1  Johns  Hopkins  Hosp.  Bull.,  1915,  xxvi,  p.  391. 


METHODS  OF  EXAMINATION  171 

two  types  of  solutions,  the  ''protected"  and  the  "non-protected." 
The  former  is  one  in  which  no  agglutination  takes  place  after  the 
addition  of  any  amount  of  any  electrolyte,  and  the  latter  is  one  in 
which  agglutination  takes  place  in  the  presence  of  very  small 
amounts  of  one  electrolyte.  It  was  then  found  that  for  practical 
purposes  a  non-protected  solution  was  one  that  would  be  completely 
precipitated  by  1.7  c.c.  of  a  1  per  cent,  sodium  chloride  solution  in 
one  hour's  time.  These  writers  further  observed  that  the  solutions 
varied  considerably  as  to  their  acidity  and  alkalinity;  that  alkaline 
solutions  were  almost  inert  to  a  positive  spinal  fluid ;  that  a  strongly 
acid  solution  gave  very  little  if  any  reaction  to  a  known  positive 
spinal  fluid  and  an  atypical  reaction  to  a  normal  fluid;  that  slightly 
acid  solutions  while  giving  a  typical  reaction  with  paretic  fluids, 
gave  a  quite  typical  reaction  in  the  so-called  luetic  zone  with  normal 
fluids,  and  only  an  intensification  of  the  reaction  with  a  fluid  from 
a  case  of  cerebrospinal  syphilis;  and  finally  that  neutral  solidions 
gave  typical  reactions  with  paretic  fluids  and  never  any  reaction  with 
normal  fluids. 

It  was  then  found  that  if  non-protected  solutions  which  were 
either  acid  or  alkaline  were  neutralized  they  fulfilled  all  requirements. 

The  following  steps  are  taken  in  neutralizing  such  solutions: 
Alizarin-red  (1  per  cent,  solution  in  50  per  cent,  alcohol)  is  used  as 
an  indicator;  with  alkaline  colloidal  gold  solutions  this  indicator 
produces  a  purplish-red  color.  Acid  solutions  give  a  lemon-yellow 
color,  while  neutral  solutions  are  yellowish  red.  Two  drops  of  the 
indicator  are  added  to  a  test-tube  containing  about  5  c.c.  of  the  gold 
solution  and  the  reaction  noted.  If  this  is  found  to  be  neutral,  the 
solution  is,  of  course,  satisfactory.  If  it  is  not  neutral,  the  test-tubes 
are  placed  in  a  rack  and  to  each  is  added  1  c.c.  of  freshly  distilled 
water.  Then  if  the  gold  solution  was  found  acid,  1  c.c.  of  |^ 
NaOH  is  added  to  the  first  tube.  If  the  solution  was  alkaline,  1  c.c. 
of  ^  HCl  is  added.  This  is  thoroughly  mixed  and  1  c.c.  with- 
drawn and  placed  in  the  second  tube  and  the  process  is  repeated 
until  the  tenth  tube  is  reached  when  1  c.c.  is  discarded  from  it. 
It  is  seen  that  the  first  tube  contains  0.5  c.c.  of  acid  or  alkali  and 
that  each  successive  tube  contains  just  one-half  the  amount  in  the 
preceding  tube.  Two  drops  of  the  indicator  and  5  c.c.  of  the  gold 
solution  are  added  to  each  tube.  The  tube  which  shows  a  neutral 
reaction  shows  the  amount  of  acid  or  alkali  necessary  to  neutralize 
5  c.c.  of  the  gold  solution,  and  the  amount  necessary  to  neutralize 
the  entire  quantity  can  readily  be  calculated.  This  should  be  added 
gradually  to  avoid  precipitation,  and  the  solution  should  be  at  least 
forty-eight  hours  old  before  neutralization. 

Performance  of  Test. — Ten  tubes  (15  mm.  x  15  cm.)  which  have 
been  thoroughly  cleansed   by  boiling   in  10  per  cent,  potassium 


172 


LABORATORY  DIAGNOSIS 


chromate  solution,  rinsed  in  distilled  water,  and  drying  in  the  hot- 
air  sterilizer,  are  used  for  each  fluid.  Into  the  first  of  these  tubes  are 
placed  1.8  c.c.  of  a  0.4  per  cent,  sodium  chloride  solution  prepared 
with  triply  distilled  water  from  a  stock  solution  (10  per  cent. 
NaCl  (Merck)  in  triply  distilled  water),  and  into  each  of  the  suc- 
ceeding tubes  is  placed  1  c.c.  Into  the  first  tube  is  placed  0.2  c.c. 
of  the  spinal  fluid,  and  thoroughly  mixed  with  the  salt  solution  by 
drawing  the  contents  into  a  pipette  and  expelling  it  two  or  three 
times.  Then  from  the  first  tube  1  c.c.  of  the  mixture  is  withdrawn, 
placed  in  the  second  tube  and  thoroughly  mixed.  This  process  is 
repeated  with  each  succeeding  tube,  the  1  c.c.  withdrawn  from  the 
tenth  tube  being  discarded.  Each  tube  now  contains  1  c.c.  and 
the  dilutions  of  spinal  fluid  vary  from  1  to  10,  1  to  20,  1  to  40,  etc., 
up  to  1  to  5120. 

To  each  tube  are  now  added  5  c.c.  of  the  reagent  and  thoroughly 
mixed.  While  the  change  of  color  in  the  tubes  often  occurs  almost 
immediately  it  is  best  to  let  them  stand  for  twelve  to  twenty-four 
hours  before  reading  the  final  results. 

The  usual  method  of  indicating  the  color  changes  is  as  follows : 

Complete  precipitation,  fluid  clear  and  colorless 5 

Almost  complete  precipitation,  fluid  pale  bluish  gray   .      .  ...  4 

Moderate  precipitation,  fluid  almost  blue 3 

Slight  precipitation,  fluid  lilac  or  purple 2 

Faint  precipitation,  fluid  reddish  blue 1 

No  precipitation,  fluid  red 0 

The  method  of  recording  the  reaction  employed  in  the  author's 
laboratory  is  to  plot  a  curve.  The  tubes  are  indicated  by  a  vertical 
column  of  numbers  and  the  type  of  color  change  by  a  horizontal 
column. 

A  negative  reaction  in  which  all  tubes  show  no  color  change  would 
be  recorded  as  follows: 


1 

2 
3 

4 

7 
8 
9 

As  stated  above,  it  is  in  paresis  and  taboparesis  that  the  most 
typical  colloidal  gold  reactions  are  found.  Grulee  and  Moody^ 
go  so  far  as  to  state  that  so  constant  and  typical  is  the  reaction  for 


1  Am.  Jour.  Dis.  Child.,  1915,  ix,  p.  19. 


> 

I— I 

w 

< 


0 

o 
o 


METHODS  OF  EXAMINATION 


173 


paresis  that  a  diagnosis  may  be  ventured  on  that  finding  alone 
without  other  clinical  or  laboratory  evidence.  With  this  extreme 
view  the  author  cannot  agree,  as  he  has  seen  a  case  of  syphilitic 
meningitis  giving  a  reaction  typical  for  paresis.  Kaplan^  reports  a 
similar  case  and  also  one  of  multiple  sclerosis  with  a  typical  paretic 
curve.  It  must  be  admitted,  however,  that  there  is  a  possibility 
of  paresis  developing  in  all  cases  of  syphilis  of  the  central  nervous 
system,  and  the  fact  remains  that  the  colloidal  gold  test  is  today  our 
greatest  aid  in  the  diagnosis  of  general  paralysis. 

A  typical  paretic  curve  which  is  self-explanatory  would  be  recorded 
as  follows: 


1- 

2  i 

3 

^'\ 

5  -^^ 

8 '       " 

9 

nl 1 1 1 1 


The  following  curve  was  recorded  in  taboparesis : 


^\^ 

\ 

. 

5    \i 

; 

2 

] 

0 

While  the  curve  of  tabes  is  not  at  all  typical  or  constant,  it  always 
is  positive  in  untreated  cases.  The  type  of  curve  is  what  is  known 
as  the  "luetic  zone,"  and  similar  reactions  are  observed  in  so-called 
cerebrospinal  syphilis. 

Such  a  curve  as  the  following  not  infrequently  is  seen  in  tabes : 


1 

3 

\ 

^ 

4 
5 
6 
7 
8 
9 
ft 

^^ 

^^^ 

'  Serology  of   Nervous   and   Mental   Diseases,    1914,   Philadelphia   and   London, 
p.  186. 


174  LABORATORY  DIAGNOSIS 

Cytology. — While  several  varieties  of  cellular  elements  are 
encountered  in  the  spinal  fluid  in  syphilitic  involvement  of  the 
central  nervous  system,  the  majority  are  small,  markedly  basophilic, 
lymphocytes.  Attempts  have  been  made  by  different  observers 
to  attach  diagnostic  significance  to  the  finding  of  different  kinds  of 
cells,  but  it  would  seem  from  our  present  state  of  knowledge,  at 
least,  that  such  an  assumption  is  unwarranted. 

Origin  of  Cytological  Elements. — Two  theories  have  been  advanced 
to  account  for  the  origin  of  the  cellular  elements  in  the  cerebro- 
spinal fluid.  The  first  is  that  they  are  blood  cells  which  have  trans- 
migrated to  the  spinal  fluid,  and  the  second  is  that  they  are  of 
histological  origin  coming  from  the  leptomeninges.  In  all  prob- 
ability the  true  explanation  of  their  origin  is  to  be  found  in  a 
combination  of  the  two  theories. 

Technic. — ^The  most  simple  and  satisfactory  method  of  counting 
the  cellular  elements  in  the  spinal  fluid  is,  after  thoroughly  shaking 
the  containing  tube,  to  place  a  drop,  undiluted,  on  a  Fuchs-Rosen- 
thal  counting  chamber  and  with  a  low-power  objective  to  count 
all  of  the  cells  present.  Quite  frequently  it  is  impossible  with  a 
low-power  objective  to  distinguish  between  lymphocytes  and  eryth- 
rocytes. Where  there  is  doubt  a  high-power  dry  objective  should 
be  employed.  Lymphocytes  show  upon  focussing  a  distinct  flatness 
and  appear  to  be  covered  with  small  dots  which  are  corrugations 
of  the  protoplasm.  Erythrocytes,  on  the  other  hand,  do  not  appear 
flat,  gradually  disappear  upon  focussing  and  even  when  old  do  not 
present  the  dotted  appearance  of  the  lymphocytes. 

The  Fuchs-Rosenthal  counting  chamber  measures  4  mm.  square 
and  0.2  mm.  deep.  The  contents  therefore  are  3.2  cubic  millimeters, 
and  to  determine  the  number  of  cells  per  cubic  millimeter  the 
total  number  counted  should  be  divided  by  3.2. 

If  a  Fuchs-Rosenthal  counting  chamber  is  not  available  the 
ordinary  Zappert  or  Turk  blood-counting  chamber  may  be  used 
with  quite  accurate  results.  The  margin  of  error  with  the  original 
Thoma-Zeiss  chamber  is  too  great  for  it  to  be  recommended  for 
this  purpose. 

Many  workers  advocate  diluting  the  spinal  fluid  in  a  blood- 
counting  pipette  with  a  staining  solution.  This,  to  the  author's 
mind,  is  an  unnecessary  procedure.  It  ma}^  however,  be  desirable, 
when  the  fluid  contains  a  very  few  red  blood  cells,  to  dilute  it  with 
an  equal  volume  of  0.5  per  cent,  acetic  acid  which  lakes  the  erythro- 
cytes. If  much  blood  is  present,  however,  even  this  expedient 
will  not  answer,  as  the  white  cells  of  the  blood  cannot  be 
distinguished  from  the  cellular  elements  originally  in  the  fluid. 
The  spinal  fluid  should  be  examined  when  fresh,  as  standing  may 
cause  disintigration  of  the  lymphocytes. 


METHODS  OF  EXAMINATION  175 

Significance  of  Pleocytosis. — Any  increase  in  the  number  of 
cellular  elements  in  the  cerebrospinal  fluid  denotes  an  inflammatory 
irritative  condition  of  the  leptomeninges,  but  is  not  necessarily 
syphilitic. 

The  highest  number  of  cells  in  syphilitic  afi'ections  of  the  central 
nervous  system  are  found  in  syphilitic  meningitis,  when  the  count 
may  run  as  high  as  1680  (Kaplan). 

Gummata  and  syphilitic  arteritis  of  the  central  nervous  system, 
on  the  other  hand,  usually  show  low  counts. 

In  paretics  the  cell  count  generally  runs  from  15  to  75  per  c.mm., 
although  the  number  may  drop  markedly  during  the  final  decline, 
or  following  a  series  of  convulsions. 

The  spinal  fluids  of  tabetics  show  the  greatest  variations,  the 
cell  counts  in  some  cases  being  normal  and  in  others  running'  up 
into  the  hundreds.    Comparatively  high  counts  are  the  rule. 

The  operation  of  spinal  puncture  will  produce  a  local  inflammation 
of  the  leptomeninges  that  will  i^e/)-  se  cause  a  pleocytosis,  so  should 
not  be  repeated  under  ten  days. 

Reduction  of  Fehling's  Solution. — All  normal  spinal  fluid  contains 
a  substance  which  will  reduce  Fehling's  solution,  but  in  certain 
pathological  conditions  this  substance  is  absent.  It  is  usually  absent 
in  epidemic  cerebrospinal  meningitis  and  occasionally  in  syphilitic 
meningitis. 

Complement -fixation  with  Spinal  Fluid. — The  technic  of  performing 
the  complement-fixation  test  with  spinal  fluid  is  the  same  as  that 
employed  with  blood  serum  except  that  larger  quantities  are  used 
and  that  it  is  never  inactivated.  It  is  the  custom  in  the  author's 
laboratory  to  employ  five  tubes  for  each  fluid,  using  0.2,  0.4,  0.6, 
0.8  and  1  c.c,  1  c.c.  is  also  used  in  the  control  tube  without  antigen. 
The  author  does  not  consider  a  slightly  positive  Wassermann 
reaction  with  1  c.c.  of  spinal  fluid  absolutely  indicative  of  syphilis, 
nor  a  negative  reaction  with  0.2  c.c.  as  excluding  syphilis,  but  he 
does  consider  an  absolutely  negative  test  with  1  c.c.  of  fluid  as 
essential  to  a  cure.  In  diagnosis  the  same  statements  apply  to  the 
spinal  fluid  Wassermann  as  were  made  concerning  the  blood  Wasser- 
mann, viz.,  that  the  reaction  must  be  interpreted  only  in  the  light 
of  clinical  evidence,  or  at  least,  in  the  light  of  other  laboratory 
findings. 

The  Wassermann  reaction  on  the  spinal  fluid  has  been  found 
positive  in  nearly  100  per  cent,  of  fully  developed  cases  of  paresis, 
even  with  small  amounts  (0.2  c.c),  and,  as  a  rule,  the  inhibition  of 
hemolysis  is  complete.  In  the  early  and  late  stages  of  paresis  it 
may  be  positive  or  negative. 

In  the  majority  of  cases  of  tabes  dorsalis  (about  80  per  cent.) 
the  spinal  fluid  reacts  negatively  to  the  Wassermann  test  with  0.2 


176  LABORATORY  DIAGNOSIS 

c.c,  but  when  large  quantities  are  employed  (1  c.c.)  it  is  positive 
in  approximately  80  per  cent,  of  cases.  In  the  late  stages  it  may  be 
negative. 

In  syphilitic  involvement  of  the  meninges  and  arteries  of  the 
central  nervous  system,  the  result  of  the  spinal  fluid  Wassermann, 
as  Head  and  Fearnsides^  have  pointed,  out  will  depend  upon  the 
location  of  the  lesion.  If  the  spinal  cord,  its  membranes  or  nerve 
roots  be  aft'ected,  the  reaction  is  usually  strongly  positive;  while  if 
the  process  be  confined  to  the  intracranial  contents,  the  reaction 
is  negative  or  weakly  positive. 

1  Brain,  1914,  xxxvii,  p.  79. 


CHAPTER  VIII. 
PROGNOSIS. 

Usually  the  first  question  asked  by  the  syphilitic  upon  being 
informed  of  the  nature  of  his  disease  is,  "Can  I  be  cured?"  In  the 
majority  of  cases  this  can  be  answered  in  the  affirmative,  although 
the  answer  should  be  qualified  by  certain  provisos,  the  principal  one 
of  which  is  that  treatment  be  followed  energetically  and  consistently. 
The  answer  also  must  be  qualified  by  the  length  of  time  the  disease 
has  existed,  the  amount  and  nature  of  the  treatment  already 
received  and  the  portions  of  the  body  involved.  Certain  other 
factors  which  are  almost  obvious  influence  the  prognosis  to  a  greater 
or  lesser  extent.  Such  are  the  general  physical  condition  of  the 
patient,  the  presence  or  absence  of  intercurrent  disease,  the  habits, 
the  use  or  abuse  of  alcohol  and  tobacco,  age,  etc.  Some  of  the 
older  writers^  have  asserted  that  spontaneous  recoveries  from 
s>T)hilis  occasionally  occur,  but  in  the  light  of  modern  knowledge 
of  the  subject  it  would  seem  that  such  recoveries  are  impossible. 
It  is  true  that  all  outward  manifestations  of  syphilis  may  disappear 
and  the  individual  seem  in  perfect  health  and  die  from  some  other 
cause,  but  nevertheless  the  treponemata  are  undoubtedly  present 
within  the  body. 

The  Wassermann  Reaction  and  Prognosis. — ^Little  prognostic  value 
can  be  attached  to  a  single  Wassermann  reaction.  If,  as  is  prob- 
ably the  case,  the  Wassermann  reaction  depends  upon  the  production 
of  a  certain  type  of  antibodies,  it  is  also  probable  that  either  these 
antibodies  combat  the  treponemata  or  that  other  antibodies  are 
produced  at  the  same  time  which  act  in  such  a  manner,  and  that  a 
strongly  positive  Wassermann  reaction,  sometimes  at  least,  may  be 
considered  as  indicative  of  a  more  favorable  outcome.  Certainly 
it  is  true  that  not  infrequently  the  cases  showing  the  strongest 
four-plus  Wassermann  reaction  are  most  amenable  to  treatment. 
On  the  other  hand,  cases  showing  the  weakly  positive  reaction  are 
sometimes  very  refractory.  However,  a  strongly  positive  Wasser- 
mann reaction  persisting  over  a  considerable  period  of  time  in  spite 
of  energetic  treatment  must  be  looked  upon  with  grave  concern. 

Chancre. — ^It  may  safely  be  said  that  practically  100  per  cent, 
of  all  chancres  are  cured,  and  even  without  treatment  the  vast 
majority  disappear  in  from  two  or  three  weeks  to  a  few  months. 

1  Lang  in  Steadman's  Twentieth  Century  Practice  of  Medicine,  New  York,  1899, 
xviii,  p.  283. 
12 


178  PROGNOSIS 

However,  the  cure  of  the  chancre  does  not  necessarily  mean  the 
cure  of  the  syphihs.  Yet  with  modern  methods  of  treatment  the 
prognosis  of  syphihs  observed  during  the  presence  of  the  chancre 
is  excellent,  and  the  earlier  the  chancre  is  seen  and  treatment  is 
instituted,  the  greater  will  be  the  prospect  of  cure.  The  mildness 
or  severity  of  the  syphilitic  process  in  the  chancre  seems  to  bear 
but  little  relation  to  the  subsequent  course  of  the  disease,  although 
quite  frequently  a  chancre  with  marked  ulceration  is  followed  by 
severe  cutaneous  manifestations.  On  the  other  hand,  a  chancre 
showing  but  little  or  no  ulceration  may  be  followed  by  an  equally 
severe  cutaneous  outbreak. 

The  location  of  the  chancre  also  bears  but  little  relation  to  the 
prognosis.  It  has  been  stated  that  the  second  incubation  period  is 
shorter  and  that  the  subsequent  course  of  the  disease  is  more 
severe  following  extragenital  than  genital  chancres.  These  con- 
tentions, however,  lack  confirmation. 

It  has  been  thought  that  the  demonstration  of  the  nature  of  the 
treponemata  found  in  the  chancre  might  be  of  prognostic  value. 
That  is,  that  certain  strains  of  organisms  have  a  predilection  for 
certain  tissues  and  the  differentiation  of  these  strains  determine 
the  likelihood  of  involvement  of  the  tissues  most  vulnerable  to  the 
strain  demonstrated  in  a  certain  chancre.  However,  in  our  present 
state  of  knowledge  such  a  differentiation  is  impossible. 

Lymphatic  Glands. — The  prognosis  of  the  glandular  enlargement 
accompanying  the  chancre  is  excellent,  as  in  the  vast  majority  of 
cases  this  enlargement  disappears  promptly  under  specific  treat- 
ment or  even  spontaneously.  The  later  adenitis  also  disappears 
with  or  without  treatment  and  no  prognostic  importance  in  regard 
to  the  syphilis  can  be  attached  to  this  condition. 

Skin  Lesions. — The  syphilodermata  are  the  most  striking  mani- 
festations of  the  syphilitic  process,  and  in  a  general  way  it  may  be 
said  that  the  prognosis  for  the  cure  of  these  lesions  is  good.  This  is 
especially  true  of  the  macular  and  papular  s;^^hilodermata,  which, 
as  a  rule,  are  self-limited  and  disappear  sooner  or  later  even  without 
treatment,  while  under  specific  therapy  the  healing  of  these  lesions 
is  sometimes  truly  marvelous  in  its  rapidity.  The  palmar  and 
plantar  papulosquamous  syphilodermata,  especially  when  occurring 
late  in  the  course  of  the  disease  should  be  excepted  from  this  state- 
ment, as  these  lesions  are  very  chronic  in  their  tendency  and  even 
with  the  most  vigorous  treatment  are  often  most  refractory. 

The  moist  papular  lesion  also  is  very  persistent  if  left  untreated, 
but,  as  a  rule,  readily  yields  to  proper  medication. 

After  healing  of  the  macular  and  papular  syphilodermata  little 
or  no  trace  of  their  presence  is  left,  although  in  some  instances  a 
pigmentation  is  noted  which  gradually  disappears. 


SYPHILIS  OF  THE  APPENDAGES  OF   THE  SKIN  179 

The  prognosis  of  the  very. rare  vesicular  and  bullous  syphilo- 
dermata  is  good  as  they  are  very  amenable  to  specifics. 

The  pustular  lesions  are  quite  persistant,  rarely  healing  spon- 
taneousl}^  although,  as  a  rule,  yielding  quite  easily  to  antisyphilitic 
treatment,  yet  if  very  extensive  and  with  deep  ulceration  may 
present  considerable  difficulty  of  cure.  The  smaller  acuminate 
pustular  lesions  may  heal  with  no  trace  left  behind  but  a  slight 
pigmentation  or  small  pits  may  remain,  while  the  larger  lesions  are 
sometimes  followed  by  atrophic  thinning  with  slight  scarring. 

The  healing  of  the  flat  pustular  syphilodermata  W!M  leave  scarring 
and  pigmentation,  depending  upon  their  extent  and  the  depth  of 
the  ulceration. 

The  nodular  syphiloderm,  except  in  rare  instances,  is  quite 
amenable  to  treatment,  but  upon  healing  leaves  more  or  less  scarring 
and  depression  depending  upon  the  depth  of  the  lesion. 

Gummata  of  the  skin  are,  \nth  the  exception  of  the  palmar  and 
plantar  papulosquamous  syphilodermata,  the  most  difficult  of  the 
skin  lesions  of  syphilis  to  cure.  Even  these  are  usually  quite  amen- 
able to  treatment,  sometimes  healing  without  ulceration,  even 
though  they  may  have  become  quite  soft.  If  specific  medication  is 
not  instituted,  gummata  of  the  skin  may  penetrate  the  underlying 
structures  and  great  destruction  of  tissue  takes  place.  The  healing 
of  a  superficial  gumma  leaves  a  dark  red  scar  of  more  or  less  depth 
which  gradually  becomes  white  in  the  centre,  although  permanently 
pigmented  at  the  periphery. 

The  prognosis  of  syphilis  when  seen  during  the  activity  of  the 
cutaneous  manifestations  will  depend  ■  upon  the  same  conditions 
as  stated  above  for  the  prognosis  of  sj^hilis  in  general,  that  is,  the 
length  of  time  which  the  disease  has  existed,  the  amount  and  nature 
of  the  treatment  already  received  and  with  the  syphilodermata  the 
extent  of  the  involvement  of  other  portions  of  the  body. 

Syphilis  of  the  Appendages  of  the  Skin. — Hair. — ^The  prognosis 
of  syphilitic  alopecia  will  depend  upon  whether  or  not  it  is  due  to 
the  presence  upon  the  hairy  parts  of  the  sj'philodermata.  If  it  is 
due  to  such  lesions,  the  alopecia  is,  as  a  rule,  permanent,  while  if 
occurring  independently,  the  hair  ^dll  generally  return  when  proper 
treatment  is  carried  out.  In  the  case  of  complete  sj-philitic  alopecia 
observed  by  the  author,  however,  the  most  vigorous  antisyphilitic 
therapy  failed  to  stimulate  the  growth  of  hair. 

Nails. — The  prognosis  of  syphilitic  onychia  and  paronychia  will 
depend  upon  the  extent  of  the  processes.  As  a  rule,  if  the  matrix 
of  the  nail  has  not  been  destroyed,  it  "uill  return  to  normal,  a  new 
nail  developing  if  the  old  one  has  been  lost,  upon  the  institution  of 
proper  therapy.  Nothing  of  prognostic  value  as  to  the  cure  of 
syphilis  can  be  deduced  from  syphilis  of  the  appendages  of  the  skin. 


180  PROGNOSIS  ) 

Mucous  Membranes. — As  with  the  syphilodermata,  so  with  the 
syphilomycodermata,  it  may  be  said  that  the  prognosis  of  their 
cure  is  good,  and  especially  is  this  so  with  the  macular  and  papular 
lesions.  The  papular  lesions  of  the  mouth,  however,  may  be 
aggravated  and  rendered  more  refractory  by  the  use  of  tobacco. 
Leukoplakia  also  may  present  great  difficulty  of  cure. 

The  gummatous  syphilomycodermata,  as  a  rule,  readily  yield  to 
specific  treatment,  although  if  left  untreated,  may  affect  the  deeper 
structures  and  cause  great  loss  of  tissue  with  marked  deformity. 

General  Symptoms. — Little  or  nothing  of  value  from  a  prog- 
nostic standpoint  can  be  learned  from  the  general  symptoms  of 
syphilis.  Marked  fever,  however,  may  be  considered  as  indicative 
of  a  severe  luetic  infection,  or  a  contamination  with  other  organisms. 

Blood. — As  with  any  anemic  condition  the  lower  the  erythrocyte 
count  and  the  percentage  of  hemoglobin,  the  graver  will  be  the 
outlook. 

According  to  Hazen^  considerable  of  prognostic  value  may  be 
learned  from  the  leukocyte  count  in  the  so-called  secondary  stage 
of  syphilis.  Those  cases  of  his  series  showing  a  high  neutrophile 
count  and  a  low  lymphocyte  count  did  not  do  well  under  treatment, 
while  when  the  conditions  were  reversed  and  the  neutrophiles 
were  low  and  the  lymphocytes  high  the  case  did  well. 

The  prognosis  of  visceral  syphilis  and  syphilis  of  the  osseous, 
muscular  and  nervous  tissues  as  well  as  that  of  the  organs  of  special 
sense  will  be  discussed  in  Part  II. 

SYPHILIS  AND  MARRIAGE. 

One  of  the  most  frequent  questions  asked  by  the  syphilitic  is, 
"Can  I  ever  marry?    And  if  so,  when?" 

In  the  pre-Wassermann  days  a  time  limit  was  usually  set  after 
which  it  was  considered  safe  for  the  syphilitic  to  marry.  Thus, 
Fournier^  stated  that  a  minimum  period  of  three  or  four  years 
following  the  chancre  devoted  to  a  most  careful  treatment  should 
elapse  before  marriage  should  be  permitted.  Keyes^  answered  the 
question  by  saying  that  a  period  of  four  years,  during  the  last  one 
of  which  no  symptoms  of  syphilis  have  been  observed  and  during 
at  least  the  last  six  months  no  treatment  has  been  taken.  He, 
however,  considered  five  years  after  the  chancre  to  be  the  safer 
limit. 

Since  the  development  of  the  Wassermann  test  most  syphilog- 
raphers  have  considered  that  permission  to  marry  should  not  be 

1  Jour.  Cut.  Dis.,  1913,  xxxi,  p.  618. 

2  Syphilis  and  Marriage,  New  York,  1882,  p.  92. 

3  Genito-urinary  Diseases  with  Syphilis,  New  York,  1894,  p.  538. 


SYPHILIS  AND  MARRIAGE  181 

given  to  a  syphilitic  while  the  Wassermann  is  still  positive,  even  in 
spite  of  the  absence  of  other  symptoms  or  lesions  of  the  disease. 

Keyes,  Jr./  states  that  this  is  no  more  warrantable  now  than  when 
we  did  not  have  the  Wassermann  reaction  and  insists  that  the 
syphilitic  may  safely  be  told  to  marry  after  five  years  of  his  disease, 
during  the  first  three  of  which  he  has  taken  treatment  and  during 
the  last  two  from  which  he  has  taken  no  treatment  and  shown  no 
symptoms.    This  in  spite  of  a  positive  Wassermann. 

With  this  view  the  author  cannot  agree.  If  we  believe  that  a 
positive  Wassermann  is  an  indication  of  the  presence  of  living 
treponemata  in  the  body,  and  we  have  every  reason  to  so  believe, 
there  certainly  is  danger  that  these  organisms  will  get  into  the  blood 
stream  and  become  the  source  of  infection. 

Most  writers  on  the  subject  of  syphilis  and  marriage  refer  only 
to  the  disease  in  men.  This  is  undoubtedly  due  to  the  fact  that 
syphilis  is  so  much  more  common  in  marriageable  men  than  in 
marriageable  women.  Nevertheless  syphilis  is  of  sufiicient  fre- 
quency in  the  latter  to  warrant  a  consideration  of  the  subject. 

Keyes^  stated  that  in  the  female  five  years  is  little  enough  time 
and  that  more  would  be  better. 

In  this  connection  the  observation  of  Graefenberg,^  who  found 
living  treponemata  in  the  secretion  from  the  cervix  of  four  syphilitic 
women,  should  be  mentioned.  Two  of  these  were  pregnant  and  all 
four  had  condylomata  of  the  vulva,  but  with  no  lesions  of  the 
cervix.  In  five  other  women  who  had  had  treatment  no  organisms 
could  be  found. 

Chase*  quotes  Mueiler  as  having  found  treponemata  in  the 
leucorrheal  and  menstrual  discharges  in  a  prostitute  who  had  been 
suspected  of  infecting  men  but  who  presented  no  symptoms  or 
lesions  of  the  disease  but  a  positive  Wassermann. 

Gellhorn  and  Ehrenfest^  found  living  treponemata  in  the  normal 
cervical  secretion  in  two  cases.  In  the  first  case  an  ulcer  of  the 
fourchette  was  present  while  the  vagina  and  cervix  were  normal. 
In  the  second  case  the  organisms  were  found  two  months  following 
the  healing  of  lesions  of  the  cervix  under  energetic  treatment. 

To  the  author  it  seems  that  permission  to  marry  should  not  be 
given,  either  to  men  or  women,  until  a  complete  cure  of  the  disease 
has  resulted.  The  standard  for  cure  will  be  discussed  in  the  chapter 
on  Treatment.  It  is  admitted  that  in  some  instances,  perhaps  in 
many,  infection  will  not  follow  the  marriage  of  syphilitics  with 

1  Jour.  Am.  Med.  Assn.,  1915,  Ixiv,  p.  804. 

2  Genito-urinary  Diseases  with  Syphilis,  New  York,  1894,  p.  538. 

3  Arch.  f.  Gynak.,  1909,  Ixxxvii,  p.  190. 

*  Texas  State  Jour.  Med.,  1913,  ix,  p.  95. 
6  Am.  Jour.  Obst.,  1916,  Ixxiii,  p.  864. 


182  .  PROGNOSIS 

positive  Wassermann  reactions,  but  certainly  it  is  safer  to  wait 
for  a  complete  serological  as  well  as  clinical  cure>  Possibly  there  are 
individuals  who  are  so  anxious  to  marry  that  they  are  willing  to 
assume  the  risk  of  infection.  Such  individuals  should  be  examined 
very  carefully  at  frequent  intervals  for  evidences  of  syphilis. 

MORTALITY. 

As  pointed  out  in  Chapter  II,  the  old  adage  that  "syphilis  never 
kills"  is  false.  However,  it  is  most  difficult  to  determine  the  true 
case  mortality  of  this  disease.  This  is  mainly  due  to  the  fact  that 
in  the  majority  of  instances  deaths  only  of  such  cases  as  exhibit 
outward  manifestations  of  syphilis  are  reported  as  such,  and  the 
true  state  of  affairs  can  be  learned  only  when  syphilis  is  ruled 
out  absolutely  as  the  cause  of  deaths  in  all  cases,  both  by  laboratory 
and  clinical  evidence  antimortem,  and  by  careful  autopsy  findings. 

Syphilis  is  essentially  a  chronic  disease,  and  undoubtedly  many 
cases  which  have  been  discharged  from  hospital  or  private  practice 
as  cured,  or  have  passed  from  observation  without  being  discharged 
are  not  cured,  and  perhaps  years  later  develop  visceral  syphilis 
and  die  from  its  effects  without  a  correct  diagnosis  being  made. 

Ravogli^  states  that  of  7824  cases  of  syphilis  in  the  Cincinnati 
City  Hospital  during  the  nineteen  years  between  1888  and  1906 
there  were  but  168  deaths.  This  gives  a  case  mortality  of  2.14 
per  cent. 

The  following  table  shows  the  number  of  cases  of  syphilis,  the 
deaths  and  the  case  mortality  of  this  disease  in  the  Canal  Zone 
during  the  seven  years  from  1907  to  1913.^ 


Case  mortality. 

Year. 

No.  cases. 

No.  deaths. 

per  cent. 

U907 

245 

2 

0.8 

1908 

143 

0 

0.0 

1909 

168 

0 

0.0 

1910 

221 

1 

0.45 

1911 

340 

1 

0.29 

1912 

544 

1 

0.18 

1913 

570 

3 

0.52 

These  figures  show  little  concerning  the  true  case  mortality  of 
syphilis. 

The  figures  from  the  Bellevue  Hospital,  New  York,^  probably 
come  nearer  revealing  the  true  state  of  affairs.  During  1911  in 
this  institution  there  were  555  cases  of  syphilis  and  44  deaths,  giving 
a  case  mortality  of  8  per  cent, 

1  Syphilis,  New  York,  1907,  p.  147. 

2  Annual  Reports,  Department  of  Sanitation  Isthmian  Canal,  Comm.,  1907-13. 

3  Annual  Report,  Bellevue  Hospital,  New  York,  1911. 


MORTALITY  '  183 

It  goes  almost  without  saying  that  death  due  directly  to  chancre, 
the  syphilodermata  or  the  syphilomycodermata  does  not  occur, 
although  it  is  conceivable  that  death  due  to  a  superimposed  bacterial 
infection  acquired  through  these  lesions  might  take  place. 

In  syphilis  of  some  of  the  viscera  and  of  the  central  nervous 
system  it  is  different  and  deaths  due  directly  to  these  conditions 
are  more  or  less  frequent.  This  will  be  fully  discussed  in  Part  II 
under  the  proper  headings. 


CHAPTER  IX. 
PROPHYLAXIS. 

The  prophylaxis  of  syphilis  presents  one  of  the  gravest  problems 
before  the  medical  profession  today.  And  yet  it  is  not  altogether 
a  medical  problem;  it  involves  the  whole  fabric  of  society,  and  its 
solution  must  rest  upon  sanitarians,  sociologists,  educators,  and 
statesmen,  as  well  as  upon  physicians. 

The  prevention  of  syphilis  is  naturally  divided  into  personal 
measures  and  public  measures. 

PERSONAL  MEASURES. 

As  the  majority  of  cases  of  syphilis  are  contracted  through 
sexual  intercourse,  the  first  and  most  effective  method  of  personal 
prophylaxis  is  the  avoidance  of  sexual  intercourse  with  anyone  not 
absolutely  above  suspicion,  in  other  woids,  the  avoidance  of  sexual 
intercourse  out  of  the  marriage  bed.  In  our  present  state  of  social 
development  this  is  of  course  an  ideal  which  cannot  be  attained. 
So  if  men  will  indulge  in  ilicit  intercourse,  some  method  of  prevent- 
ing the  spread  of  venereal  disease,  and  especially  syphilis,  must 
be  adopted.  It  has  been  said  that  one  who  indulges  his  sexual 
passions  illicitly  deserves  the  penalty  of  venereal  disease.  This 
might  be  all  well  enough  if  the  offender  were  the  only  one  to  suffer, 
but  every  syphilitic  becomes  at  least  a  potential  source  of  danger 
to  many  others.  It  is  therefore  the  duty  of  physicians  to  prescribe 
prophylactic  measures  for  patients  who  desire  them. 

Probably  the  best  and  safest  method  of  preventing  the  spread 
of  syphilis  through  sexual  intercourse  is  the  use  of  the  so-called 
"condom."  This  will  prevent  the  spread  of  the  disease  from  either 
party  affected.  Ablutions  with  antiseptic  liquids  such  as  weak 
solutions  of  potassium  permanganate  by  both  parties  both  before 
and  after  intercourse  is  also  quite  efficacious. 

One  of  the  most  widely  practised  prophylactic  measures  is  the 
use  of  calomel  ointment  (calomel  20,  lanolin  40)  as  advocated  by 
Metchnikoff  and  Roux  and  proved  by  animal  and  human  experi- 
mentation an  absolute  preventative  of  syphilis  if  used  within  one 
hour  after  inoculation  and  almost  always  a  sure  preventative  if 
used  within  six  hours  after  exposure. 


PUBLIC  MEASURES  185 

The  thorough  application  of  Neisser's  paste  to  the  parts  within 
a  few  hours  after  intercourse  is  probably  better.  This  paste  has 
the  following  composition: 

Hydrarg.  chlor.  corrosivi 0.3 

Sodii  chloridi 1.0 

Tragacanth 2.0 

Amylum ■ 4.0 

Gelatini 7.0 

Alcoholis 25.0 

Glycerini 17.0 

Aquae q.  s.  ad  100.0 

Circumcision  has  been  advocated  as  a  prophylactic  measure  for 
syphilis,  but  to  the  author's  mind  this  seems  a  rather  useless  pro- 
cedure, as  he  has  seen  many  chancres  in  the  circumcised  as  well 
as  in  the  uncircumcised.  Purely  as  a  measure  of  cleanliness  and  as 
a  prophylaxis  of  masturbation  in  the  young  circumcision  is  highly 
to  be  recommended. 

The  prophylaxis  of  genital  and  perigenital  chancres  not  acquired 
through  sexual  acts  rests  upon  care  in  using  public  toilets. 

Chancres  of  the  lips,  tongue,  tonsil,  etc.,  are  to  be  prevented  by 
avoiding  promiscuous  kissing,  the  use  of  eating  utensils,  drinking 
cups,  pipes,  etc.,  after  others. 

Physicians  could  remove  absolutely  the  danger  of  chancre  of 
the  fingers  by  the  use  of  rubber  gloves  in  all  procedures  in  which 
there  is  any  possibility  of  infection.  And  in  fact  if  personal  pro- 
phylaxis could  be  systematically  employed,  syphilis  could  be 
stamped  out  in  a  comparatively  short  time. 

It  has  been  hoped  that  a  vaccine  or  a  serum  might  be  found  which 
would  immunize  the  individual  against  syphilis.  But  up  to  the 
present  time  no  such  prophylactic  has  been  produced,  although  it 
is  well  within  the  range  of  possibility.  In  fact  Zinnser,  Hopkins 
and  McBurney^  have  shown  that  the  sera  of  rabbits  and  sheep 
immunized  with  cultures  of  Treponema  pallidum  acquire  tre- 
ponemacidal  properties  for  the  cultivated  organisms,  although  the 
normal  sera  of  these  animals  possesses  such  properties  but  to  a 
lesser  degree.  In  a  subsequent  paper,^  however,  it  has  been  shown 
that  immune  sera  exert  practically  no  action  upon  virulent  organ- 
isms obtained  directly  from  lesions.  Nevertheless  these  authors 
do  not  feel  discouraged  and  state  that  the  work  is  being  continued. 

PUBLIC   MEASURES. 

Regulation  of  Prostitution. — Prostitution  is  as  old  as  civilization, 
and  volumes  have  been  written  upon  its  social,  its  moral,  and  its 
medical  aspects.  It  is  not  within  the  scope  of  this  work  to  deal 
with  prostitution  in  all  its  phases,  nor  to  discuss  the  various  methods 

1  Jour.  Exper.  Med.,  1916,  xxiii,  p.  323.  2  Ibid.,  p.  341. 


186  PROPHYLAXIS 

of  regulation  which  have  been  tried.  But  the  author  does  wish  to 
state  that  in  his  opinion  some  regulation  of  prostitution  with  regular 
medical  inspection  of  prostitutes  will  greatly  reduce  the  prevalence 
of  syphilis.  Americans  are  prone  to  turn  their  backs  on  the  prob- 
lems of  prostitution,  to  ignore  its  existence,  and  to  consider  its 
recognition  by  law  as  an  admission  on  the  part  of  the  State  that  it 
cannot  be  eradicated.  Therefore  in  most  American  cities  prosti- 
tution is  regulated  by  a  system  of  fines  and  bribes,  or  "hush  money" 
paid  to  the  police  for  their  protection,  and  no  medical  inspection 
is  made. 

A  number  of  cities  have  closed  all  houses  of  prostitution.  This 
has  undoubtedly  but  served  to  increase  the  amount  of  clandestine 
prostitution,  and  it  is  a  well-known  fact  that  syphilis  is  more  pre- 
valent among  this  class  of  prostitutes  than  among  the  inmates  of 
regular  houses.  If,  however,  the  houses  are  in  reality  kept  closed, 
this  measure  certainly  diminishes  the  total  amount  of  prostitution. 
Its  effect  upon  youths  is  especially  good,  as  not  infrequently  such 
are  lead  into  beginning  the  practice  of  illicit  intercourse  by  being 
taken  to  houses  of  prostitution  by  older  men,  and  if  there  are  no 
such  houses,  they  cannot  be  taken  to  them.  It  is  also  a  well-known 
fact  that  prostitution  and  the  use  of  alcohol  are  closely  interwoven, 
so  to  a  considerable  extent  the  problem  of  prostitution  becomes 
the  problem  of  prohibition. 

Education. — Education  is  a  great  factor  in  the  prophylaxis  of 
syphilis.  Most  youths  when  they  begin  a  life  of  licentiousness 
do  not  realize  the  danger  to  which  they  are  exposed.  They  have 
been  told  that  a  "dose  of  clap  is  no  worse  than  a  bad  cold,"  and 
perhaps  know  nothing  of  syphilis.  Further,  they  have  been  led 
to  believe  that  sexual  intercourse  is  a  necessity  to  their  health. 
If  all  the  young  men  of  the  land  could  be  taught  that  continence 
is  entirely  compatible  with  health,  and  that  in  indulging  themselves 
they  are  being  exposed  to  diseases  which  not  only  may  cause  them 
great  suffering  but  may  remain  with  them  throughout  life,  and  may 
lead  them  to  an  early  death,  a  great  advance  in  the  prophylaxis 
of  syphilis  would  have  been  made.  This  brings  up  the  question 
of  the  best  means  of  bringing  about  such  education.  Should  young 
men  be  taught  sex  hygiene  in  the  home,  in  the  school,  by  the 
church,  or  by  the  family  physician?  It  seems  to  be  the  consensus  of 
opinion  of  the  majority  of  workers  along  this  line  that  the  home  is 
the  proper  place  for  such  knowledge  to  be  taught.  However, 
with  the  vast  majority  of  parents,  even  if  they  do  recognize  the 
need,  this  is  no  easy  matter,  and  they  must  be  taught  the  impor- 
tance to  the  child  of  such  instruction  and  how  best  to  impart  it. 
This  could  readily  be  accomplished  by  public  lectures  or  visits  to 
the  home  by  district  nurses.  There  are  also  many  pamphlets  and 
books  dealing  with  these  problems  which  could  be  circulated. 


PUBLIC  MEASURES  187 

Education  alone  will  not  solve  the  problem  of  the  prophylaxis 
of  syphilis,  at  least  there  are  other  means  at  hand  which  can  be 
employed  which  would  stamp  out  the  disease  long  before  all  the 
young  men  of  the  land  could  be  taught  the  folly  of  illicit  intercourse 
and  be  persuaded  to  refrain  from  indulging  in  it. 

Legislation. — The  segregation  of  all  syphilitics  during  the  infective 
stage  would,  of  course,  stamp  out  the  disease,  but  in  our  present 
state  of  social  development  this  is  impossible. 

Syphilis,  however,  should  be  made  a  reportable  disease,  and  a  severe 
penalty  should  be  imposed  upon  physicians  for  not  reporting  cases. 

Wassermann  surveys  of  the  inmates  of  all  prisons,  eleemosynary 
institutions,  etc.,  should  be  made.  All  immigrants  should  be  care- 
ully  examined  for  evidence  of  syphilis,  including  a  Wassermann 
test,  and  if  found  luetic,  should  be  denied  entrance  to  the  country. 
All  applicants  for  civil  service  positions  should  be  compelled  to 
have  Wassermann  tests,  and  if  found  positive  should  not  be  given 
employment.  From  this  it  would  not  be  a  far  cry  to  persuading 
employers  in  all  lines  to  compel  their  employees  to  present  a  clean 
bill  of  health  in  regard  to  syphilis. 

A  marriage  license  should  not  be  granted  to  anyone  without  a 
thorough  physical  examination  and  a  negative  Wassermann  reac- 
tion showing  the  probable  absence  of  syphilis.  These  examinations 
should  be  made  by  the  city  or  county  physicians,  and  for  a  nominal 
charge. 

When  prostitution  is  permitted  at  all  it  should  be  under  strict 
surveillance  and  regular  medical  inspection,  including  a  Wassermann 
reaction  of  all  prostitutes,  should  be  made. 

By  these  procedures,  especially  making  syphilis  a  reportable 
disease,  it  would  not  be  long  before  the  health  authorities  would 
have  a  fairly  complete  knowledge  of  the  prevalence  of  syphilis 
in  a  given  community. 

With  this  accomplished  all  syphilitics  should  be  forced  to  take 
treatment,  from  private  physicians  if  they  prefer  or  from  the  city 
or  county  physicians,  until  they  are  cured.  The  standard  of  cure 
should  be  fixed  by  law  arid  all  patients  compelled  to  conform  to 
it.  A  severe  penalty  should  be  imposed  on  those  failing  to  report 
for  treatriaent. 

During  the  time  when  infection  through  intermediate  contact 
is  most  likely  to  occur,  all  patients  whose  employment  makes  them 
especially  dangerous  to  others  should  be  compelled  to  stop  work. 
This  in  the  majority  of  cases  would  not  be  for  long. 

The  author  is  aware  that  such  drastic  procedures  as  have  been 
outlined  would  be  extremely  costly,  but  the  benefit  to  be  derived 
could  not  be  estimated  in  dollars  and  cents.  Undoubtedly  if  such 
methods  were  employed,  in  a  few  years  syphilis  would  be  as  rare 
as  smallpox,  and  eventually  be  wiped  off  the  face  of  the  earth. 


CHAPTER  X. 

TREATMENT. 

With  a  disease  so  protean  in  its  manifestations  as  syphilis  it 
may  well  be  said  that  each  case  is  more  or  less  of  a  law  unto  itself. 
Therefore,  as  no  two  cases  are  exactly  alike  the  treatment  must  be 
made  to  conform  to  each  individual  case.  There  are,  however, 
certain  general  factors  which  enter  into  the  management  of  all 
cases.  The  treatment  of  syphilis  may  be  divided  into  general, 
specific,  and  symptomatic. 

GENERAL   TREATMENT. 

Hygienic. — The  importance  of  the  hygienic  treatment  of  syphilis 
is  hardly  to  be  overestimated.  Too  many  physicians  are  prone 
to  rely  solely  upon  the  specifics  and  totally  disregard  hygienic 
measures.  The  author  does  not  wish  to  minimize  the  importance 
of  the  syphilitic  specifics,  for  without  them  syphilis  could  not 
be  cured;  but  he  does  wish  to  emphasize  the  importance  of  proper 
hygiene  in  the  control  of  this  disease.  It  goes  almost  without  say- 
ing that  sanitary  surroundings  are  most  desirable  for  all  syphilitics, 
and  the  author  is  of  the  opinion  that  hospitalization  is  to  be  recom- 
mended when  possible.  Not  only  should  the  surroundings  of  the 
syphilitic  be  sanitary,  but  they  should  be  pleasant  and  congenial. 
The  life  of  the  syphilitic  should  be  very  regular;  regular  sleep, 
regular  meals,  a  certain  amount  of  regular  exercise,  depending  upon 
the  individual,  should  be  insisted  upon.  He  should  not  overwork, 
and  above  all  he  should  not  worry.  He  should  have  plenty  of 
diversion,  with  outdoor  exercise,  such  as  golf,  when  not  contra- 
indicated. 

The  use  of  alcohol  in  any  form  should  be  totally  interdicted,  and 
the  patient  should  be  warned  that  even  small  amounts  are  detri- 
mental In  fact,  it  is  probably  better  for  the  syphilitic  to  get  com- 
pletely intoxicated  once  or  twice  a  year  and  totally  abstain  in  the 
meantime  than  to  drink  even  very  moderately  all  the  time.  The 
use  of  tobacco  is  to  be  curtailed  as  much  as  possible,  especially 
should  this  be  done  in  cases  with  lesions  of  the  mouth  and  throat. 
The  syphilitic  should  be  warned  against  sexual  excesses,  and  of 
course  during  the  infective  stages  should  not  be  permitted  to  indulge 
his  sexual  appetite  under  any  circumstances. 


GENERAL   TREATMENT  189 

Dietetic, — Little  can  be  said  concerning  the  dietetic  treatment  of 
syphilis,  as  no  special  diet  is  required  except  in  gastric  and  intestinal 
syphilis,  and  perhaps  in  syphilitic  nephritis.  Certain  general  rules, 
however,  should  be  followed.  Overeating  certainly  should  not  be 
indulged  in,  and  the  quality  of  the  food  should  be  good. 

Hydrotherapeutic; — ^Almost  from  time  immemorial,  baths,  espe- 
cially baths  in  water  from  natural  hot  springs,  have  had  a  great 
reputation  in  the  treatment  of  syphilis,  and  many  syphilitics  have 
journeyed  each  year  to  the  great  watering  places  of  the  world, 
especially  Aix-la-Chappelle  in  Europe  and  the  hot  springs  of 
Arkansas  in  this  country.  The  latter  have  probably  held  the  fore- 
most place  both  in  the  minds  of  the  laity  and  medical  profession 
as  a  mecca  for  syphilitics  in  America. 

The  hot  springs  of  this  resort  are  located  upon  the  United  States 
Government  Reservation,  and  the  use  of  the  water  from  them  is 
controlled  by  the  Department  of  the  Interior.  The  water  from  the 
springs  varies  in  temperature  from  35.2°  C.  (95.4°  F.)  to  63.9°  C. 
(147°  F.),  and  according  to  the  analyses  made  by  Haywood^  the 
chemical  composition  of  the  water  from  the  various  springs  is 
practically  the  same. 

The  following  are  the  figures  for  the  so-called  Big  Iron  Spring, 
the  largest  of  the  group,  which  has  a  flow  of  201,600  gallons  per 
day. 

Parts  per  Million. 

Si02 45.59 

SO4  . 7.84 

HCO3 168.10 

NO3 0.44 

NO2 0.0016 

PO4 0.05 

As04 None 

BO2 1.29 

CI 2.53 

Br ' trace 

I w trace 

Fe 


Al   / 0-1^ 

Mn   .      .      .    • 0.34 

Ca 46.93 

Mg 5.10 

K 1.60 

Na 4.76 

Li trace 

NH4 .'      .      .      .  0.04 

Boltwood^  found  that  the  waters  from  the  hot  springs  as  well 
as  those  from  one  of  the  cold  springs  of  the  vicinity  possess  con- 
siderable radio-activity,  the  highest  amount  found  being  265  Mache 

1  Analyses  of  the  Waters  of  the  Hot  Springs  of  Arkansas,  Washington,  1912,  p.  34. 

2  Am.  Jour.  Med.  Sc,  1905,  xx,  p.  128. 


190  TREATMENT 

units.  This  amount,  according  to  Hammeter  and  Zueblin/  is 
higher  than  that  recorded  for  any  other  spring  in  this  country. 

The  benefits  to  the  syphiHtic  derived  from  a  sojourn  and  a  course 
of  treatment  at  Hot  Springs  have  variously  been  ascribed  to  a 
specific  action  of  the  waters,  both  as  baths  and  taken  internally,  to 
the  greater  elimination  produced,  to  stimulation,  to  the  routine 
life,  and  to  the  effects  of  the  salubrious  climate.  The  alleged 
specific  effect  of  the  waters  has  been  said  to  be  due  to  some  peculiar 
chemical  combination  of  the  solids  in  solution,  to  electricity  pro- 
duced by  chemical  decomposition,  to  a  peculiar  heat  with  which 
they  are  imbued,  and  latterly  to  the  radio-activity  which  they 
have  been  shown  to  possess. 

Keyes^  says  of  the  Arkansas  hot  springs:  "The  hot  springs  of 
Arkansas  require  a  word  of  serious  comment  here.  That  they  have 
a  positive  value,  I  am  sure.  I  visited  the  springs  a  few  years  ago 
and  remained  there  long  enough  to  see  their  workings.  I  have  sent 
many  patients  there,  have  deterred  many  others  from  going,  and 
seen  patients  in  all  stages  of  syphilis  who  had  been  to  the  springs 
before  their  first  visit  to  me.  From  such  premises  I  think  I  may 
reach  conclusions  which  shall  be  reasonably  just.  The  physicians 
who  practise  at  the  springs  are  not  in  accord  as  to  the  special 
property  of  the  waters  which  gives  them  their  value.  Some  think 
that  the  water  is  like  any  other  hot  water,  and  that  patients  do  well 
at  the  springs  simply  because  they  come  there  determined  to  take 
care  of  themselves  and  to  make  the  treatment  of  their  malady  their 
first  object.  True  it  is  that  the  waters  are  almost  void  of  any 
mineral  ingredient.  The  waters  of  the  so-called  Old  Iron  Spring 
(I  think  it  is  called  so  because  the  house  erected  over  it  is  made  of 
corrugated  iron  and  not  because  of  the  iron  in  its  water)  deposit 
a  tuft  which  clings  in  masses  to  the  hill  out  of  which  the  spring 
flows,  but  I  am  informed  that  the  actual  mineral  contents  of  the 
water  is  only  about  eight  grains  to  the  gallon,  which  is  practically 
nothing.  Lime  seems  to  be  the  main  ingredient.  The  water  of 
this  spring  is  used  at  the  main  hotel  of  the  place  for  drinking  water, 
and  it  is  as  pure,  bright,  sparkling,  and  tasteless  as  any  water  I 
have  ever  seen.  Taken  cold,  it  certainly  has  no  obvious  effect; 
taken  hot,  it  is  diuretic  and  diaphoretic  more  positively  than 
ordinary  hot  water.     It  does  not  nauseate. 

"Others  of  the  local  physicians  impute  the  effect  of  the  waters 
to  something  sui  generis  in  the  quality  of  the  heat  they  contain; 
others  to  electricity,  in  which  also  the  water  is  said  to  abound.  My 
own  investigations  showed  me  that  a  foot-bath    at  110°  F.  was 

1  Arch.  Int.  Med.,  1915,  xv,  p.  188. 

2  The  Surgical  Diseases  of  the  Genito-urinary  Organs,  Including  Syphilis,  New 
York,  1894.  p.  553. 


GENERAL   TREATMENT  191 

impossible.  The  feet  could  not  possibly  be  retained  in  water  of 
that  temperature,  a  thing  perfectly  possible  (but  not  pleasant) 
at  home  in  croton  water.  A  thermometer  held  in  the  mouth  while 
making  the  attempt  to  take  this  foot-bath  was  raised  to  103°  F. 
An  ordinary  bath  at  98°  F.  was  unpleasantly  hot  and  caused  the 
perspiration  to  trickle  from  the  face  in  streams.  The  immediate 
after-effect  of  the  bath  (unlike  that  of  an  ordinary  hot  bath)  is  one 
of  exhilaration,  followed  in  a  couple  of  hours  by  reaction  and  a 
desire  to  sleep.  The  immediate  effect  of  the  water  I  found  to  be 
stimulating,  not  soothing.  An  inflamed  joint  soaked  in  this  water 
is  harmed  by  it  and  the  pain  intensified,  contrary  to  what  is  expe- 
rienced with  ordinary  hot  water;  acute  eruptions  are  said  to  be 
aggravated  by  the  water.  This  I  did  not  personally  have  an  oppor- 
tunity of  testing  except  in  a  case  of  generalized  eczema,  which 
certainly  was  aggravated  at  the  hot  springs,  and  began  to  get  well 
at  the  (cold)  sulphur  potash  spring  a  few  miles  away.  Old  chronic 
ulcers,  whether  scrofulous,  syphilitic,  or  accidental,  are  stimulated 
promptly  into  granulation  by  the  local  effect  of  these  waters.  The 
appetite  improves  under  their  use  and  the  ordinary  functions  seem 
to  be  performed  better  than  when  they  are  not  used  by  the  visitors 
to  the  place.  The  uterine  function  seems  to  be  stimulated  by  the 
baths,  and  stories  of  a  return  of  menstruation  after  the  change  of 
life,  of  impregnation  after  long  sterility,  and  the  like,  are  told  by 
the  natives.  Paralytics,  and  people  recovering  from  apoplexy, 
seem  to  thrive  at  the  springs. 

"But  all  this  is  not  the  cure  of  syphilis,  and  my  observation 
showed  me  plainly  that  the  physicians  who  did  well  at  the  springs 
used  most  unsparingly  mercury  by  inunction  and  iodide  of  potas- 
sium internally  in  enormous  doses.  And  this  is  exactly  wherein 
the  value  of  the  springs  seems  to  lie.  Patients  broken  down,  cach- 
ectic, with  faulty  stomachs,  who  have  syphilitic  lesions  which  fail 
to  yield  at  home  because  they  cannot  tolerate  a  sufficiently  high 
degree  of  medication,  these  are  the  patients  to  send  to  the  hot 
springs.  There,  under  the  assistance  of  the  hot  water  internally 
and  the  baths,  they  can  take  a  mercurial  friction  day  after  day, 
without  salivation,  which  would  overwhelm  them  at  home,  and  their 
doses  of  iodide  of  potassium  can  be  quadrupled  without  upsetting 
the  stomach.  I  have  verified  this  over  and  over  again.  This  is 
the  only  class  of  patients  I  ever  send  to  the  springs — those  requir- 
ing stiff  medication  for  serious  lesions  who  cannot  at  home  be  made 
to  tolerate  a  sufficiently  high  dose  to  pull  them  through. 

"I  could  multiply  illustrative  cases  of  this  order  almost  indef- 
initely. One  patient,  several  years  ago,  I  sent  to  the  springs  under 
escort  of  a  nurse  and  a  relative.  He  had  been  going  persistently  out 
of  his  mind  while  under  my  treatment  and  that  of  several  other  physi- 


192  TREATMENT 

cians.  He  had  had  several  hemiplegic  attacks,  serious  ocular 
troubles,  aphasia,  double  vision,  and  mental  derangement.  His 
mind  was  useless  for  all  purposes  and  he  was  obliged  to  give  up  busi- 
ness entirely.  No  efforts  of  mine  or  others  could  by  any  of  the  adju- 
vants, belladonna,  arsenic,  milk,  carbonated  water,  alkaline  water, 
get  the  daily  dose  of  this  patient  above  300  grains  of  the  iodide 
of  potassium — and  his  symptoms  were  gradually  gaining  upon  him 
until  his  case  seemed  hopeless.  Then  he  went  with  difficulty  to 
the  springs,  and  there,  with  no  aid  beyond  the  use  of  the  waters, 
his  daily  dose  of  the  iodides  was  run  up  to  800  grains,  and  under 
this  he  recovered,  and  by  after-treatment  at  home  became  able 
again  to  resume  his  business.  I  have  had  a  number  of  cases  of  this 
sort,  and,  particularly  when  the  brain  and  cord  are  seriously 
involved,  I  advocate  the  hot  springs  at  any  price  in  money,  time, 
or  comfort.  It  is  certainly  worth  while.  But  for  ordinary  syphilis 
I  do  not  consider  the  springs  of  any  value.  They  do  not  shorten 
the  duration  of  the  disease,  prevent  relapse,  or  cure  it  in  any  sense. 
The  lesions  of  early  syphilis  disappear  rapidly  under  the  heavy 
medication  administered  at  the  springs,  but  I  do  not  think  there 
is  any  special  value  in  this,  because  it  makes  the  patient  less  willing 
to  take  prolonged  continuous  treatment,  in  which  alone,  in  my 
opinion,  lies  his  best  hope." 

White^  has  this  to  say  concerning  the  class  of  patients  who  should 
be  sent  to  the  hot  springs: 

"1.  The  patients  whose  mode  of  life  is  objectionable  and  who 
cannot  be  controlled  while  under  home  or  other  customary  influ- 
ences. This  includes  not  only  the  large  class  of  hard  drinkers, 
who  are  apt  also  to  use  tobacco  too  freely  and  to  indulge  in  various 
other  excesses,  but  also  the  much  smaller  class  whose  excessive 
devotion  to  work  or  business  interferes  with  their  general  health 
and  lessens  their  strength  and  vitality. 

"2.  Patients  whose  symptoms  resist  full  doses  of  the  specific 
drugs  and  who  are  unable  to  take  larger  doses  without  a  break- 
down of  the  digestive  apparatus,  or  the  production  of  mercurial 
or  iodic  intoxication.  Those  especially  should  be  sent  who  have 
involvement  of  the  viscera  and  still  more  particularly  if  the  brain 
or  spinal  cord  is  affected. 

"3.  Patients  who  with  syphilis  have  intense  syphilophobia  and 
require  the  mental  impression,  and  in  addition  the  tonic  influence 
of  change  of  scene  and  climate. 

"4.  Patients  with  defective  elimination  or  with  marked  idio- 
syncrasy as  regards  either  mercury  or  the  iodides." 

1  Morrow:  System  of  Geni to-urinary  Diseases,  Syphilology,  and  Dermatology, 
New  York,  1898,  ii,  p.  786. 


GENERAL  TREATMENT  193 

Fordyce,  who  resided  in  Hot  Springs  for  three  years,  says  in  part 
as  quoted  by  White  :^ 

"  It  would  be  quite  rational  to  suppose  that  the  increased  tissue 
change  which  hot  baths  are  known  to  produce  could  be  utilized 
to  advantage  in  combating  a  new  growth  of  such  unstable  character 
as  the  neoplasms  of  syphilis;  and,  in  fact,  the  last  stages  of  the 
disease  seem  to  be  especially  benefited  by  the  use  of  the  baths  in 
connection  with  specific  remedies.  How  much  of  the  cure  depends 
upon  the  increased  power  of  digestion  and  assimilation  caused  by 
the  change  of  air,  scene,  and  diet,  and  how  much  on  the  baths, 
is  difficult  to  say.  I  have  seen,  however,  patients  in  a  profound 
state  of  cachexia  from  old  syphilis  improve  rapidly  at  the  springs, 
patients  who  had  been  in  charge  of  competent  physicians  at  home, 
and  who  had  taken  mercury  and  iodide  of  potassium  to  the  limit 
of  tolerance." 

From  the  above  it  would  seem  that  there  is  no  doubt  of  the 
benefit  to  the  syphilitic  derived  from  a  sojourn  and  course  of 
treatment  at  Hot  Springs. 

That  the  waters  of  the  hot  springs  possess  any  specific  action  on 
the  Treponema  pallidum  the  author  does  not  believe.  It  is  a  fact, 
however,  that  patients  bathing  in  these  waters  are  able  to  take 
much  more  mercury  without  any  untoward  effects  than  others.  It 
is  furthermore  highly  probable  that  some  of  the  benefits  derived  are 
due  to  increased  elimination  of  the  products  of  catabolism.  To 
these  benefits  derived  from  the  increased  ability  to  take  mercury 
and  the  increased  elimination  must  be  added  the  benefits  derived 
from  the  regular  life  the  patient  usually  leads,  the  outdoor  exercise, 
the  freedom  from  business  cares  and  worries,  and  finally,  the  fact 
that  the  average  patient  who  comes  to  this  or  any  other  resort 
follows  the  physician's  directions  more  implicitly  than  when  at 
home;  in  short,  makes  a  business  of  getting  well. 

While  each  case  of  syphilis  is  a  law  unto  itself  in  regard  to  bathing 
as  well  as  in  other  features,  the  following  may  be  said  to  be  fairly 
representative  of  the  usual  method  of  administering  the  baths  to 
syphilitics  in  this  resort: 

The  patient  is  placed  in  a  tub  of  the  hot  water  at  a  temperature 
of  35.5°  C.  to  38°  C.  (96°  F.  to  100°  F.)  where  he  remains  from  eight 
to  fifteen  minutes.  When  free  diaphoresis  is  desired  he  is  placed 
in  a  hot  wet  pack  and  covered  with  blankets  for  fifteen  to  thirty 
minutes,  and  when  more  profuse  sweating  is  wanted  the  vapor 
cabinet  is  used  for  three  to  five  minutes  Usually  in  the  tub  and 
in  the  pack  the  hot  water  is  taken  to  drink  to  assist  in  promoting 
diaphoresis.     Generally  following  the  pack  a  shower  and  needle 

1  Morrow:  System  of  Genito-urinary  Diseases,  Syphilology,  and  Dermatology, 
New  York,  1898,  ii,  p.  788. 

13 


194  TREATMENT 

is  given  for  two  or  three  minutes  beginning  at  a  temperature  of 
38°  C.  (100°  F.)  and  being  reduced  to  32°  C.  or  27°  C.  (90°  F.  or 
80°  F.) .  Following  this  the  patient  sits  or  lies  in  the  cooling  room 
until  cool  and  the  skin  is  dry.  Ordinarily  the  patient  spends  from 
one  and  a  half  to  two  and  a  half  hours  at  the  bath  house. 

Tonic. — A  great  many  syphilitics  are  more  or  less  cachectic 
and  anemic,  and  quite  frequently  need  tonic  treatment.  It  is  also 
true  that  following  a  severe  course  of  treatment,  patients  are  some- 
times found  to  have  lost  weight  and  are  greatly  benefited  by  tonics. 

The  author  has  been  in  the  habit  of  prescribing  in  such  cases  a 
tonic  similar  to  the  following: 

I^ — Tinct.  nucis  vom 45 . 0 

Tinct.  cardamom,  comp., 

Glycerini aa       90.0 

Aquae q.  s.  ad     240.0 

M.  et  Sig. — From  one  to  two  teaspoonfuls  in  water  before  each  meal. 

SPECIFIC   TREATMENT. 

There  are  two  known  specifics  for  syphilis,  mercury  and  arsenic, 
and  according  to  some  a  third,  iodin. 

Mercury. — According  to  Buret^  the  Chinese  as  far  back  as  2637 
B.C.  prescribed  mercurial  frictions  in  the  treatment  of  syphilis. 
Whether  or  not  this  is  true,  it  is  a  fact  that  Fracastor^  wrote  in  1530 
concerning  the  use  of  mercury  in  syphilis  as  follows: 

''As  a  fact,  the  action  of  mercury  on  the  scourge  is  marvelous, 
either  because  its  natural  affinity  for  heat  and  cold  renders  it  proper 
to  absorb  the  devouring  fire  of  the  disease;  or,  because  its  surpris- 
ing density  permits  it  to  divide  and  to  dissolve  the  humors  for  a 
reason  that  is  analogous  to  that  which  gives  to  incandescent  iron 
a  caustic  action  more  marked  than  that  of  a  light  flame;  or  that  its 
mobile  and  penetrating  molecules,  apt  to  infiltrate  themselves  in 
the  warp  of  tissues,  have  the  power  of  pursuing  and  consuming 
even  to  the  bottom  of  organs  the  impure  yeasts  of  the  disease; 
or  finally  that  its  magic  virtues  are  derived  from  some  occult  force 
whose  mystery  escapes  us." 

From  the  day  of  Fracastor  to  now  mercury  in  some  form  or  other 
has  been  used  in  the  treatment  of  syphilis,  and  in  spite  of  the  newer 
arsenic  preparations  has  held  its  own  with  the  vast  majority  of 
physicians  as  a  specific. 

Methods  of  Administration. — Mouth. — Probably  the  most  fre- 
quently used  method  of  administering  mercury  is  by  mouth,  and 
it  is  also  the  easiest  and  most  convenient  method.     Numerous 

1  Syphilis  in  Ancient  and  Prehistoric  Times,  American  edition,  Philadelphia, 
1891,  p.  61. 

2  Syphilis,  St.  Louis,  1911,  p.  35. 


SPECIFIC  TREATMENT  195 

preparations  of  mercury  have  been  used  in  this  manner,  the 
principal  ones  of  which  are  the  gray  powder,  the  protiodide,  the 
bichloride,  blue  pill,  and  calomel. 

Gray  Powder  (hydrargyrum  cum  creta)  is  employed  most  exten- 
sively in  England  and  is  usually  prescribed  in  the  form  of  a  pill 
of  0.065  gram  (1  grain).  Numerous  schedules  for  its  administration 
have  been  used,  but  the  one  adopted  by  the  Royal  Army  Medical 
Corps^  seems  to  be  the  most  popular. 

This  plan  of  treatment  covers  a  course  of  nearly  two  years,  and 
is  as  follows: 

First  course:  Months.  Pills. 

One  month,  taking  six  pills  a  day 1  180 

Interval  of  three  days  without  taking  pill. 

One  month,  taking  four  pills  a  day    ......  1  120 

Interval  of  seven  days. 

One  month,  taking  three  pUls  a  day '      1  90 

Interval  of  one  month 1 

Second  Course: 

Three  months,  taking  three  pills  a  day 3  270 

Interval  of  one  month 1 

Third  Course: 

Three  months,  taking  two  pills  a  day 3  180 

Interval  of  one  month 1 

Fourth  Course: 

Three  months,  taking  one  pill  daily  ......  3     .  90 

Interval  6f  three  months 3 

Fifth  Course: 

Three  months,  taking  one  pill  daily 3  90 

21  1020 

Protiodide  {hydrargyrum  iodidum  viride  or  hydrargyrum  iodium 
fiavum). — This  is  the  form  of  mercury  most  frequently  employed 
in  France  as  well  as  in  this  country  for  internal  administration.  It 
also,  as  a  rule,  is  given  in  pill  form  and  in  doses  of  0.008  to  0.05 
gram  (|  to  f  grain)  after  each  meal.  In  the  rare  cases  in  which 
the  author  prescribes  mercury  by  mouth  the  usual  dose  is  0.016 
gram  (|  grain).  In  weak,  debilitated  individuals  and  in  women 
this  may  be  too  large  a  dose,  while  men  of  robust  constitution  may 
be  able  to  stand  as  much  as  0.05  gram  (f  grain).  However,  it  is 
always  well  to  start  with  the  smaller  doses.  If  after  a  few  days 
no  evident  improvement  has  taken  place  and  no  untoward  effects 
are  noted  the  dosage  may  gradually  be  increased  every  two  or  three 
days  by  0.004  to  0.008  gram  (xg-  to  |  grain)  until  the  maximum 
dose  of  0.05  gram  (|  grain)  is  reached,  or  until  improvement  is  seen 
when  the  dose  may  remain  stationary  until  toxic  effects  are  noted. 

Bichloride  {hydrargyrum  chloridum  corrosimim)  is  seldom  used 
alone,  owing  to  its  toxic  effect  and  irritative  action  on  the  mucous 

1  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  ii,  p.  190. 


196  TREATMENT 

membranes  of  the  mouth  and  throat.  It  is  very  frequently  pre- 
scribed with  small  doses  of  opium  and  usually  forms  the  mercurial 
portion  of  the  so-called  mixed  treatment  to  be  described  later. 
The  continued  use  of  opium  with  mercury  is  never  to  be  recom- 
mended, as  there  is  too  much  danger  of  the  opium  habit  being 
formed. 

Ravogli^  recommends  very  highly  the  so-called  Liquor  of  Van 
Swieten  which  has  the  following  formula: 

I^ — Hydrarg.  bichlorid.  corros 0.90 

Alcohol 96.00 

Aq.  destillat 928.00 

This  he  prescribes  in  tablespoonful  doses,  well  diluted  in  water 
after  breakfast,  and  after  the  evening  meal,  thus  giving  the  patient 
0.025  gram  (|  grain)  of  the  bichloride  per  day.  Ravogli  claims  never 
to  have  seen  any  untoward  effects  of  this  medication. 

Blue  pill  {inassa  hydrargyri)  has  had  considerable  vogue  in  the 
treatment  of  syphilis.  It  usually  is  prescribed  in  0.065  gram  (1 
grain)  doses,  but  owing  to  its  great  tendency  to  produce  ptyalism 
has  little  to  recommend  it. 

Calomel  (hydrargyrum  chloridum  mite)  while  formerly  extensively 
employed  in  the  treatment  of  syphilis  is  today  rarely  if  ever 
administered  by  mouth  as  a  specific  in  this  disease. 

Other  forms  of  mercury  which  are  sometimes  administered  by 
mouth  as  mentioned  by  Lambkin^  are  the  tannate,  the  corbolate, 
the  peptonate,  the  salicylate,  the  acetate,  the  sozoiodolate,  and 
mercuric  cholate. 

Inunctions. — The  use  of  mercury  by  inunction  is  probably  the 
oldest  method  of  administering  this  drug  in  the  treatment  of  syphilis. 
As  pointed  out  above,  Buret^  states  this  procedure  was  employed  by 
the  Chinese  as  far  back  as  2637  B.C.  Be  that  as  it  may,  there  is  no 
doubt  but  that  it  was  employed  in  Europe  at  an  early  date,  as 
the  writings  of  the  physicians  of  the  sixteenth  century  abound  in 
references  to  the  use  of  mercurial  ointments,  and  although  this 
method  of  treating  syphilis  fell  somewhat  into  disrepute,  it  was 
revived  from  time  to  time  and  today  constitutes  one  of  the  most 
frequently  used  methods  of  administering  mercury. 

The  preparation  most  generally  employed  is  the  official  blue 
ointment  (unguentum  hydrargyrum),  although  various  substitutes 
have  been  used,  such  as  unguentum  cinereum,  vasogen  mercurial 
ointment,  etc. 

The  average  amount  used  for  one  treatment  is  4  grams  (1  dram) 

1  Syphilis,  New  York,  1907,  p.  188. 

2  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  ii,  p.  193. 

'  Syphilis  in  Ancient  and  Prehistoric  Times,  American  edition,  Philadelphia,  1891, 
p.  61. 


SPECIFIC   TREATMENT   "  197 

and  the  rubbing  can  be  done  either  by  the  patient  himself  or  by 
another.  As  usually  prescribed  the  patient  is  instructed  to  take 
a  hot  bath  before  retiring,  or  if  this  is  impossible  the  portion  of 
the  body  which  is  to  be  rubbed  is  washed  with  soap  and  water  and 
carefully  dried.  The  ointment  is  then  smeared  on  and  thoroughly 
rubbed  into  the  skin  with  the  hands,  using  a  circular  movement 
for  twenty  to  twenty-five  minutes.  When  the  rubbing  is  complete 
most  of  the  ointment  should  have  disappeared.  Following  the 
inunction  the  patient  puts  on  a  shirt  or  pair  of  drawers,  depending 
upon  the  part  rubbed,  which  he  uses  continuously  for  a  week,  and 
over  this  his  regular  sleeping  garments. 

Each  physician  usually  has  his  own  schedule  for  the  part  selected 
for  the  rubbings,  although  the  order  is  immaterial.  The  following 
schedule  is  very  satisfactory: 

First  night.     Inner  surfaces  of  right  thigh. 
Second  night.    Inner  surface  of  left  thigh. 
Third  night.    Inner  surface  of  right  arm. 
Fourth  night.     Inner  surface  of  left  arm. 
Fifth  night.    Abdomen. 
Sixth  night.    Right  side  of  thorax. 
Seventh  night.     Left  side  of  thorax. 
This  schedule  is  then  repeated  as  frequently  as  necessary. 
As  employed  in  Hot  Springs  inunctions  are,  as  a  rule,  given  by 
a  professional  "mercury  rubber,"   who   uses   a  rubber  mit  or  a 
mechanical  apparatus,  and  the  back  is  always  the  seat  of  the 
application.     (See  Fig.  72.) 

The  blue  ointment  is  prescribed  in  what  are  locally  known  as 
"fours,"  "sixes,"  "eights,"  etc.,  and  signifies  that  one  ounce  of 
the  ointment  is  divided  into  four,  six,  or  eight  equal  parts,  one  part 
being  used  for  each  inunction. 

The  patient  usually  takes  his  bath  some  time  after  breakfast 
then  repairs  to  the  "rubbing  parlor,"  where  the  inunction  is  given. 
The  patient  sits  astride  a  chair  facing  the  back,  folds  his  arms  on 
it  and  places  his  chin  on  his  arms,  the  rubbing  continuing  for 
twenty  to  twenty-five  minutes.  He  then  puts  on  a  thin  undershirt, 
which  is  used  as  a  "mercury  shirt"  for  one  week  without  change, 
the  inunction  usually  being  given  daily. 

The  treatment,  as  a  rule,  is  continued  until  signs  of  ptyalism 
are  noted. 

Plasters. — ^IVIercurial  plasters  of  various  kinds  have  been  employed, 
probably  the  most  famous  being  the  emplastrum  de  Vigo  invented 
by  John  of  Vigo.  This  was  a  complicated  mixture  containing  as 
well  as  the  mercury  such  ingredients  of  witchcraft  as  fat  of  the 
viper,  frogs,  and  worms^  to  which  latter  were  principally  ascribed 
the  beneficial  results. 


198  TREATMENT 

Quinquad/  in  1890,  proposed  a  plaster  with  the  following  formula: 

Emplast.  diachyli. 3000  parts 

Hydrarg.  chloridi  mite  1000     " 

01.  ricini 300     " 

For  its  general  effect  this  was  applied  on  linen,  usually  over  the 
spleen  and  locally  to  various  lesions. 

Fumigation. — The  treatment  of  syphilis  by  mercury  vapor  for- 
merly was  employed  quite  extensively,  but  is  little  used  today, 
except  in  the  local  treatment  of  some  of  the  syphilodermata. 

The  method  consists  of  covering  the  body,  with  the  exception 
of  the  head,  with  a  specially  devised  cabinet  or  tent  or  with  blankets, 
the  patient  sitting  on  a  cane-bottom  chair.  The  mercury,  usually 
calomel,  is  then  burned  by  placing  it  over  an  alcohol  lamp.  The 
heat  from  the  lamp  soon  excites  perspiration  and  the  vapor  of  the 
calomel  clings  to  the  body.  The  treatment  is  usually  continued 
twenty  minutes,  with  the  lamp  burning  and  ten  minutes  allowed 
for  cooling  after  the  lamp  is  extinguished. 

Hypodermic. — Hebra,^  in  1861,  probably  was  the  first  to  employ 
hypodermic  injections  of  mercury  in  the  treatment  of  syphilis. 
This  investigator  used  injections  of  the  bichloride  and  treated 
two  patients.  In  1864  Scarenzio^  reported  the  use  of  calomel  in 
this  manner,  while  Berkley  Hill,*  in  1863,  reported  the  injection  of 
eleven  cases  with  bichloride.  It  was  not,  however,  until  after  the 
appearance  of  Lewin's^  work,  in  1869,  that  the  hypodermic  treatment 
of  syphilis  became  at  all  popular.  Since  that  time  this  method 
of  medication  has  been  used  most  extensively,  and  many  different 
preparations  of  mercury  have  been  employed.  It  will  be  impos- 
sible even  to  mention  all  of  the  preparations  of  mercury  which  have 
been  recommended  for  hypodermic  use  in  the  treatment  of  syphilis, 
but  the  most  important  ones  will  be  described. 

At  first  the  injections  were  all  given  subcutaneously  and  some- 
times frightful  abscesses  followed,  but  according  to  Lambkin,^ 
Balzer,  in  1888,  pointed  out  the  advantages  of  deep  intramuscular 
injections,  and  since  that  time  this  method  has  grown  in  favor  until 
today  it  is  practised  almost  to  the  exclusion  of  the  subcutaneous 
route. 

The  preparations  of  mercury  used  for  the  hypodermic  treatment 
of  syphilis  may  be  divided  into  the  soluble  preparations  and  the 
insoluble  preparations. 

1  Bull.  Soc.  franc,  de  dermat.  et  de  syph.,  1890,  p.  63. 

2  Allgemeine  wiener  med.  Zeitung,   1861,   No.  30. 

3  Annali   di   Medicina,   August   and   September,    1864. 

4  Lancet,  1866,  i,  p.  498. 

5  Behandlung  der  Syphilis  mit  subcutanen  Sublimat-injectionen,  Berlin,  1869. 
8  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  ii,  p.  281. 


SPECIFIC   TREATMENT  199 

Insoluble  Preparations. — Metallic  mercury  was  first  used  by 
Furbringer/  in  1879,  who  used  a  mixture  of  metallic  mercury, 
2  parts;  mucilage  of  acacia  with  glycerin,  10  parts.  While  this 
method  was  given  a  trial  by  some  other  investigators,  by  most  of 
them  it  received  but  scant  approval. 

Gray  oil  {oleum  cinereum),  which  is  in  reality  a  preparation  of 
metallic  mercury,  was  introduced  into  the  therapy  of  syphilis  in 
1884  by  Lang.^  According  to  this  author  the  preparation  of  gray 
oil  is  as  follows:  A  certain  amount  of  lanolin  is  dissolved  in  a 
large  quantity  of  chloroform  and  while  still  in  the  fluid  state  double 
the  quantity  of  metallic  mercury  is  added  and  thoroughly  triturated. 
During  the  latter  process  the  chloroform  evaporates,  leaving  the 
so-called  unguentum  cinereum  lanulatum  forte,  which  as  will  be 
seen,  is  an  ointment  consisting  of  two  parts  of  mercury  and  one 
part  of  lanolin. 

By  adding  1  part  of  olive  oil  or  liquid  paraffin  to  3  parts  of  this 
basic  ointment  the  50  per  cent,  oleum  cinereum  is  prepared.  This 
contains  0.81  gram  per  cubic  centimeter  and  is  given  in  doses  of 
0.05  c.c.  or  0.04  gram  of  metallic  mercury. 

The  "course"  as  recommended  by  Lang  consists  of  eight  to 
twelve  doses  given  at  first  every  second  or  third  day  but  later,  as 
improvement  is  noted,  every  five  or  eight  days. 

The  oleum  cinereum  should  be  kept  in  a  wide-mouthed,  glass- 
stoppered  bottle  and  in  a  cool  place,  and  when  used  is  warmed  and 
thoroughly  shaken. 

Lambkin's  Mercurial  Cream. — This  preparation  of  metallic  mer- 
cury proposed  by  Lambkin^  has  the  following  formula : 

Hydrargyrum  pur 10  grams 

"Creo-camph." equal  parts 

Solute  creosote  and  camphoric  acid 20  c.c. 

Palmitin  basis  to 100  c.c. 

Each  cubic  centimeter  of  this  preparation  contains  0.1  gram  of 
metallic  mercury  or  10  minims  contain  1  grain.  According  to 
Lambkin,  injections  are  to  be  made  on  an  average  of  once  a  week 
in  doses  of  10  minims. 

Calomel. — This  salt  of  mercury  was,  as  stated  above,  one  of  the 
first  to  be  used  hypodermically  in  the  treatment  of  syphilis. 
Scarenzio  employed  it  suspended  in  glycerin  or  mucilage  of  acacia 
and  injected  0.4  gram  (6  grains)  in  two  doses,  eight,  ten,  fourteen, 
or  twenty-one  days  apart,  and  considered  this  amount  sufiicient 

1  Deutsch.  Arch.  f.  kHn.  med.,  1879,  xxiv,  p.  129. 

2  Stedman:  Twentieth  Century  Practice  of  Medicine,  New  York,  1899,  xviii, 
p.  312. 

^  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  ii,  p.  292. 


200  TREATMENT 

for  a  cure.     The  injections  were  almost  invariably  followed  by 
abscesses,  but  apparently  were  not  considered  serious. 

Lambkin^  has  proposed  a  preparation  containing  calomel  similar 
to  his  mercurial  cream,  which  has  the  following  formula: 

Calomel 5  grams 

"Creo-camph." 20  c.c. 

Palmitin  basis  to 100  c.c. 

It  will  be  seen  that  each  cubic  centimeter  of  this  preparation 
contains  0.05  gram  of  calomel  while  10  mininis  contain  ^  grain. 
The  dose  recommended  is  10  to  15  minims  once  a  week  for  not 
more  than  four  wrecks  in  succession. 

The  salicylate  has  been  employed  quite  extensively  both  by 
mouth  and  by  hypodermic  injection.  When  administered  hypo- 
dermically  it  is  usually  suspended  in  some  oily  liquid. 

Candler^  proposed  the  following  formula,  which  has  given  excel- 
lent results  in  the  hands  of  the  author:  10  per  cent,  mercury  salicy- 
late in  albolene  oil,  plus  1  grain  of  novocain  to  the  ounce.  The 
dose  is  1  c.c.  which  contains  0.1  gram  (1|  grains)  of  the  mercury 
and  0.002  gram  (^  grain)  of  the  novocain. 

The  author  'RTites  the  following  prescription  for  this  preparation: 

I^ — Hydrarg.  salicylat 3.0 

Albolin  (sterUized) ■" 30.0 

Novocaiu 0.065 

Other  Tnsoluhle  Preparations. — Numerous  other  insoluble  prepa- 
rations of  mercury  have  been  recommended  from  time  to  time  for 
the  treatment  of  syphilis,  and  usually  have  been  heralded  by  their 
exploiters  as  superior  to  all  others.  The  most  important  of  these 
are  the  yellow  oxide,  the  black  oxide,  the  yrotoiodide,  the  thymolace- 
tate,  the  tannate,  the  sulphate,  the  yelloio  sulphate,  and  the  red 
sulphate 

Soluble  Preparations. —  The  bichloride,  as  stated  above,  was 
probably  the  first  preparation  of  mercury  to  be  administered 
hypodermically,  and  is  also  the  most  extensively  used  of  the  soluble 
salts  in  the  treatment  of  syphilis.  It  is  usually  given  in  doses  of 
0.005  gram  (yj  grain)  to  0.048  gram  (f  grain)  daily  or  every  other 
day. 

The  following  prescription,  each  cubic  centimeter  of  which 
contains  0.02  gram  (y%  grain),  may  be  used: 

IJ — Hydrarg.  chlorid.  corrosiv. 2.0 

Sodii  chlorid 1.0 

Aquae  destillat 100.0 

1  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  ii,  p.  294. 
-  Jour.  Michigan  Med.  See,  1915,  xiv,  p.  225. 


SPECIFIC   TREATMENT  201 

The  henzoate  is  only  slightly  soluble  in  water,  but  upon  the 
addition  of  sodium  chloride  readily  dissolves.  This  preparation 
was  first  used  by  Stukobenkoff/  and  has  been  employed  quite  exten- 
sively since.  The  author  uses  the  following  formula,  which  has 
proved  very  satisfactory: 

I^ — Hydrarg.  benzoat 2.0 

Sodii  chloric! 2.-5 

Aqu£e  sterilat 100.0 

The  initial  dose  is  0.5  c.c,  which  contains  0.01  gram  (^  grain) 
of  the  mercury. 

The  succinimide  is  one  of  the  most  popular  of  the  soluble  salts 
of  mercury  for  the  hypodermic  injection  in  syphilis.  It  is  readily 
soluble  in  water  and  is  procurable  in  convenient  tablet  form  from 
the  various  pharmaceutical  houses.  The  usual  dose  is  0.013  gram 
(i  grain),  is  given  daily,  and  may  be  increased  as  high  as  0.05 
gram  (4  grain) . 

To  overcome  the  pain  which  sometimes  is  observed  following 
the  injection  of  the  succinimide  the  author  has  been  in  the  habit 
of  using  a  solution  of  this  salt  to  which  has  been  added  0.5  per  cent, 
of  beta-eucaine  as  follows: 

I^ — Hydrarg.  succinimid 2.6 

Beta-eucaine 0..5 

Aquse 100.0 

It  will  be  seen  that  each  \  c.c.  contains  0.013  gram  (4  grain) 
of  the  salt,  which  is  the  usual  dose,  but  which  may  be  increased 
to  2  c.c 

The  hiniodide  {hydrargyrum  iodidum  riihrum). — According  to 
Power-  this  preparation  of  mercury  was  first  used  by  Panas  in  the 
proportion  of  4  cgms.  of  the  salt  to  10  c.c.  of  sterilized  oil.  It  is 
also  prepared  under  various  proprietary  names  and  has  given  verv' 
good  satisfaction  in  the  hands  of  the  author. 

The  cyanide,  which  has  been  employed  quite  extensively,  was 
introduced  as  a  hypodermic  injection  for  sj'philis  by  Cullingworth.^ 
It  is  usually  prescribed  with  some  form  of  analgesic,  such  as'  cocain, 
acoin,  beta-eucaine,  etc. 

The  technic  of  administration  is  the  same  whether  the  soluble 
or  insoluble  preparations  are  used.  An  all-glass  syringe  is  much  to 
be  preferred,  and  either  a  gold  or  a  platinum-iridium  needle  is 
desirable,  as  steel  needles  are  amalgamated  by  the  mercury.  The 
needle  should  be  sharp,  as  there  is  much  less  pain  when  a  sharp 

1  Vrac,  1884,  iv,  p.  9.3. 

2  System  of  Syphilis,  London,  1909,  ii,  p.  2-3.5. 

3  Lancet,  1874,  i,  p.  653. 


202  TREATMENT 

needle  is  used  than  accompanies  the  use  of  a  dull  one.  The  size 
of  the  needle  should  not  exceed  20-gauge  and  for  the  soluble  mercury 
salts  in  watery  solution  a  much  smaller  needle  may  be  used.  The 
length  should  be  about. 5  cms.  (2  inches),  and  longer  for  very  fleshy 
individuals. 

If  the  syringe  is  used  for  nothing  but  the  hypodermic  injections 
in  the  treatment  of  syphilis  and  the  same  mercurial  preparation 
is  employed,  it  is  not  necessary  to  sterilize  it  between  injections  if 
it  is  kept  where  it  will  be  free  from  dust.  The  needle,  however, 
should  be  sterilized  before  and  after  each  injection.  The  site  of 
injection  is  usually  the  buttock,  although  the  pectoral,  the  deltoid, 
or  the  muscles  of  the  interscapular  region  may  be  employed.  The 
injections  are  to  be  given  on  alternate  sides  of  the  body,  and  about' 
2  cm.  should  separate  the  injections  on  the  same  side. 

It  is  imperative  to  avoid  piercing  important  structures,  so  the 
actual  site  of  injection  should  be  chosen  with  care.  Galliot's  rule 
is  the  simplest  guide  for  injections  in  the  buttock.  A  line  is  drawn 
vertically  at  the  junction  of  the  inner  and  middle  thirds  of  the 
buttock,  while  another  line  is  drawn  horizontally  two  finger- 
breadths  above  the  top  of  the  great  trochanter.  The  intersection 
of  the  two  lines  and  points  above  and  to  the  outer  side  of  it  may  be 
used  with  impunity. 

The  injections  may  be  made  with  the  patient  standing  or  lying. 
The  site  of  injection  should  be  painted  with  iodin  and  the  needle 
plunged  directly  into  the  muscle  with  a  swift  stroke.  When  the 
needle  is  in  position  the  plunger  of  the  syringe  is  withdrawn  slightly 
to  ascertain  if  a  vein  has  been  pierced.  If  such  is  the  case,  blood 
will  appear  in  the  syringe  and  the  needle  should  be  withdrawn  and 
a  new  site  selected.  If  no  blood  is  seen,  the  dose  is  slowly  injected 
and  the  needle  withdrawn  with  a  swift  jerk,  to  avoid  leaving  any 
of  the  mercurial  preparation,  which  may  have  remained  in  the 
needle,  in  the  subcutaneous  tissues.  The  author  massages  the  spot 
gently  for  two  or  three  minutes,  which  assists  in  the  absorption  of 
the  mercury  (if  a  soluble  salt)  and  renders  the  pain  less  severe. 
Usually  no  dressing  is  necessary,  although  a  drop  of  collodion  may 
be  applied. 

Comparative  Value  of  Various  Preparations. — The  insoluble  prepa- 
rations of  mercury  are  to  be  desired  in  certain  cases,  owing  to  the 
infrequency  with  which  it  is  necessary  to  administer  them,  thus 
making  the  visits  to  the  physician  less  frequent.  Of  the  insoluble 
preparations,  calomel  is  the  most  efficient,  but  causes  more  pain 
than  the  gray  oil.  Lambkin's  preparation  of  calomel,  however, 
may  be  injected  with  comparative  freedom  from  pain.  The  injec- 
tion of  the  salicylate  prepared  after  Candler's  formula  also  usually 
is  practically  painless. 


SPECIFIC   TREATMENT  203 

The  disadvantages  of  the  insoluble  preparations  of  mercury  lie 
in  the  danger  of  them  causing  embolism  and  mercurial  poisoning 
from  accumulation  and  that  their  action  is  slower  than  that  of  the 
sol  uble  preparations.  The  former  should  not  occur  if  the  precautions 
outHned  above  in  the  technic  of  injection  are  observed.  The  pre- 
vention of  mercurial  poisoning  by  the  injection  of  the  insoluble 
preparations  of  mercury  is  sometimes  impossible,  as  the  drug  is 
so  slowly  absorbed  that  a  large  quantity  may  be  left  at  the  site 
of  injection  after  the  beginning  of  symptoms  and  can  be  removed 
only  by  excision.  This  is  a  difficult  and  serious  procedure,  and  is 
to  be  recommended  only  in  case  of  the  most  urgent  nature. 

Recent  experiments^  seem  to  show  that  the  salicylate,  at  least, 
has  little  or  no  effect  on  the  Wassermann  reaction  even  when  given 
over  a  considerable  period  of  time,  and  to  the  point  of  tolerence, 
although  active  manifestations  of  syphilis  may  disappear  under 
its  use. 

The  advantages  of  the  soluble  preparations  of  mercury  are  that 
they  are  usually  less  painful  than  the  insoluble,  that  their  action 
is  quicker,  owing  to  the  fact  that  they  are  more  readily  absorbed, 
thus  reducing  the  danger  of  mercury  poisoning  to  a  minimum; 
and  when  the  latter  does  occur  it  can  be  stopped  much  more  readily 
than  when  the  insoluble  preparations  are  used. 

The  disadvantage  of  the  soluble  preparations  is  that  they  must 
be  given  more  frequently. 

In  the  author's  practice,  which  consists  almost  entirely  of 
visitors  to  Hot  Springs  who  come  here  with  the  sole  object  in  view 
of  getting  well,  the  soluble  preparations  are  invariably  used,  for 
it  has  been  found  that  the  majority  of  patients  much  prefer  to  visit 
the  physician  daily  for  their  injections.  They  also  want  as  quick 
results  as  possible,  and  as  the  soluble  preparations  act  more  quickly 
than  the  insoluble  ones,  the  former  are  employed  exclusively. 

The  choice  of  the  various  soluble  preparations  is  largely  a  matter 
of  personal  preference,  although  undoubtedly  some  of  the  salts 
are  more  toxic  than  others,  depending  upon  the  actual  mercury 
content.  It  sometimes  happens  that  with  one  salt  the  patient 
complains  of  more  pain  than  with  another,  so  it  may  be  advisable 
to  change  if  much  pain  is  complained  of. 

The  salt  most  frequently  employed  by  the  author  is  the  benzoate 
in  the  formula  given  above.  This  preparation  rarely  causes  pain, 
produces  quick  results,  and  is  only  slightly  toxic.  The  succinimide 
and  the  cyanide  formerly  were  used  by  the  author  quite  extensively, 
but  he  found  a  considerable  number  of  his  patients  developed  a 
slight  nephritis  after  only  a  small  quantity  had  been  administered. 

1  See  page  243. 


204  TREATMENT 

This  untoward  effect  has  been  observed  with  benzoate  in  but  one 
case,  and  this  only  after  0.4  gram  (6  grains)  had  been  given. 

Intravenous. — This  method  of  administering  mercury  in  syphihs 
was  first  practised  by  Bacelli^  in  1893,  and  has  been  used  by  many 
other  investigators.  In  this  country,  Bernart,^  Crume,^  Lydston,^ 
Kingsbury  and  Bechet,^  Stukes,^  and  others  have  practised  this 
method  with  more  or  less  success.  However,  it  never  has  come 
into  general  use,  owing  probably  to  the  comparative  difficulty  of 
the  technic. 

The  bichloride  is  the  most  frequently  used  salt,  and  is  given 
in  doses  varying  from  0.005  gram  (yV  grain)  to  0.045  gram  {-j-o 
grain).  The  cyanide,  the  biniodide,  the  benzoate,  and  sublamine 
have  also  been  used.  The  usual  method  of  procedure  is  to  dissolve 
the  salt  in  5  to  12  c.c.  of  freshly  distilled  water,  or  in  a  like  amount 
of  normal  salt  solution,  and  inject  directly  into  one  of  the  veins  of 
the  elbow  by  means  of  a  hypodermic  syringe  and  needle. 

Most  of  the  investigators  using  this  method  have  reported  more 
or  less  phlebitis  and  periphlebitis,  even  to  the  extent  of  obliteration 
of  the  vein.  The  author  has  overcome  this  to  a  certain  extent  by 
using  two  20  c.c.  syringes  and  the  specially  constructed  three- 
way  cock  devised  for  the  administration  of  neosalvarsan  in  con- 
centrated solution^  (see  Fig.  54),  and  following  the  injection  of  the 
mercury  with  10  to  15  c.c.  of  normal  salt  solution.  Even  with  this 
precaution  these  unpleasant  results  sometimes  follow.  However, 
the  author  has  been  able  completely  to  eliminate  phlebitis  by  inject- 
ing mercurialized  serum.  This  was  suggested  by  Byrne's^  article 
on  the  intradural  administration  of  mercurial  serum  in  the  treatment 
of  cerebrospinal  syphilis. 

The  method  of  procedure  is  as  follows:^  From  40  to  50  c.c.  of 
blood  are  collected  by  venipuncture  and  placed  in  a  large  test- 
tube  which  has  been  autoclaved.  After  separation  the  serum  is 
poured  off  and  thoroughly  centrifugalized.  A  watery  solution  of 
mercuric  chloride  is  prepared  so  that  each  cubic  centimeter  con- 
tains 22  mgs.  (§  grain)  of  the  salt.  The  serum  is  now  measured  and 
divided  into  two  parts,  one-third  of  the  amount  placed  in  one  tube 
and  the  remainder  in  another.  The  mercury  solution  is  added 
to  the  first  part  in  the  proportion  of  1  c.c.  to  each  2  c.c.  of  serum. 
A  heavy  precipitate  of  albuminate  of  mercury  appears  which  is 
completely  dissolved  on  the  addition  of  the  remainder  of  the  serum. 

1  Gaz.  Med.  Roma.  1893,  xix,  p.  241. 

2  New  York  Med.  Jour.,  1909,  xc,  p.  693. 

3  Jour.  Am.  Med.  Assn.,  1909,  li,  p.  2155. 

4  Ibid.,  1907,  xlix,  p.  1662.  ^  Ibid.,  1914,  Ixiii,  p.  563. 
s  .Jour.   Med.  Assn.,   Georgia,   1915. 

^  Thompson:  Jour.  Cut.  Dis.,  1915,  xxxLii,  p.  631. 

8  Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  p.  2182. 

9  Thompson:  Ibid.,  1915,  Ixiv,  p.  1471. 


SPECIFIC  TREATMENT  205 

It  will  be  seen  that  the  mixtiy-e  contains  22  mgs.  (|  grain)  of 
mercuric  chloride  in  each  7  c.c.  At  first  there  was  great  difficulty 
found  in  keeping  the  albumiriate  of  mercury  in  solution  for  any 
length  of  time,  and  it  was  necessary  to  prepare  the  solution  fresh 
before  each  injection;  but  later  it  was  discovered  that  if  the  mix- 
ture is  heated  in  the  water-bath  for  one-half  hour  at  55°  C.  (131° 
F.)  it  will  remain  in  solution  indefinitely.  It  is  not  necessary  to 
use  autogenous  serum.  Blood  may  be  collected  from  any  individual 
and  the  mercurialized  serum  prepared  and  kept  in  sealed  ampules. 

The  injections  are  made  into  one  of  the  veins  at  the  elbow  with 
an  all-glass  syringe  and  a  20-gauge  needle.  It  is  imperative  that 
the  needle  be  sharp.  A  tourniquet  is  applied  above  the  elbow  until 
the  veins  stand  out  prominently.  The  field  is  sterilized  with  alco- 
hol and  the  needle  inserted  in  the  direction  of  the  blood  stream, 
into  the  most  prominent  vein.  A  slight  flow  of  blood  into  the  syringe 
will  indicate  that  the  needle  is  within  the  lumen  of  the  vein.  The 
tourniquent  is  removed  and  the  serum  slowly  injected.  A  drop  of 
collodion  is  placed  on  the  wound. 

The  initial  dose  is  1.75  c.c.  or  5  mgs.  (yV  grain)  of  mercury, 
and  is  increased  to  7.  c.c.  or  22  mgs.  (^  grain). 

Nixon^  has  proposed  a  method  for  intravenous  injection  of 
mercury  which  is  highly  satisfactory,  and  owing  to  its  simplicity 
has  recently  been  employed  by  the  author  more  frequently  than  the 
injection  of  mercurialized  serum.  However,  instead  of  injecting  the 
mercury  simply  dissolved  in  water,  as  Nixon  advises,  the  following 
method  is  employed :  A  2  per  cent,  solution  of  bichloride  or  benzoate 
of  mercury  is  prepared.  When  an  injection  is  to  be  made  a  20  c.c. 
Luer  syringe  is  filled  to  the  10  c.c.  mark  with  sterile  normal  salt 
solution  and  the  plunger  removed.  The  dose  of  mercury  is  then 
measured  with  a  graduated  pipette  and  dropped  into  the  barrel  of 
the  syringe.  The  plunger  is  replaced,  the  solution  thoroughly 
mixed,  and  the  air  expelled.  The  needle  (No.  19-gauge  is  most 
satisfactory)  is  then  inserted  into  a  prominent  vein  at  the  elbow, 
traction  made  on  the  plunger  until  10  c.c.  of  blood  have  been  with- 
drawn and  mixed  with  the  mercury  solution,  when  the  entire 
quantity  of  blood  and  mercury  is  reinjected. 

By  withdrawing  the  blood  into  the  syringe  it  mixes  with  the 
mercury  and  forms  an  albuminate  which  is  non-corrosive  and  does 
not  cause  phlebitis. 

The  use  of  salt  solution  instead  of  water  obviates  the  danger  of 
hemolysis. 

Suppositories. — This  method  of  administrating  mercury  was 
advocated    by    Audry,'    who    employed    suppositories    containing 

1  Jour.  Am.  Med.  Assn.,  1916,  Ixvi,  p.  1622. 

2  Ann.  de  dermat.  et  de  syph.,  1905,  vi,  p.  793. 


206  TREATMENT 

gray  oil  and  cocoa  butter.  These  he  used  with  varying  amounts 
of  gray  oil  so  that  they  would  contain  from  0.02  to  0.04  gram  of 
mercury.  A  suppository  is  inserted  into  the  rectum  nightly  for  a 
month,  when  treatment  is  discontinued  for  four  or  five  days,  after 
which  it  is  again  resumed. 

Precautions  in  Administering  Mercury. — Owing  to  the  marked 
tendency  of  mercury  to  produce  stomatitis,  the  greatest  care  should 
be  exercised  in  the  hygiene  of  the  mouth.  Before  beginning  the 
administration  of  this  drug  the  patient  should  be  sent  to  a  com- 
petent dentist  and  have  his  teeth  treated,  including  the  filling 
of  cavities,  the  removing  of  old  stumps,  and  a  thorough  cleansing. 
If  pyorrhea  exists,  it  should  be  determined  by  microscopic  exam- 
ination if  the  Endameba  buccalis  is  present,  and  if  so  some  emetine 
should  be  administered. 

During  mercurial  treatment  all  particles  of  food  should  be 
removed  from  between  the  teeth  with  dental  floss  and  they  should 
be  brushed  carefully  after  each  meal  with  some  good  dentifrice. 
A  mouth  wash  should  also  be  used  frequently  during  the  day.  This 
may  consist  simply  of  4  per  cent,  solution  of  potassium  chlorate. 
A  little  peppermint-water  may  be  added  to  this  or  the  following 
prescription  may  be  used: 

I^ — Potass,  chloratis 10.0 

Tinct.  myrrhse 15.0 

Aquae  camphorse q.  s.  ad     250.0 

The  urine  should  be  examined  at  frequent  intervals  for  evidence 
of  nephritis. 

Contraindications. — That  the  use  of  mercury  in  syphilis  is  ever 
absolutely  contraindicated  is  doubtful.  There  are,  however,  cer- 
tain conditions  in  which  its  use  should  be  attended  with  the  greatest 
care  and  perhaps  entirely  withheld  temporarily. 

In  acute  infectious  fevers  complicating  syphilis  mercury  should 
be  used  only  sparingly  if  at  all  during  the  febrile  stage. 

In  tuberculosis  associated  with  syphilis  mercury  should  be  given 
in  minute  doses  and  its  action  carefully  watched,  as  any  untoward 
symptoms  developing  from  its  use  would  have  an  unfavorable 
effect  on  the  course  of  the  tuberculosis.  However,  if  by  admin- 
istering mercury  the  syphilis  can  be  overcome,  the  tuberculosis 
should  be  favorably  influenced. 

Nephritis  is  probably  the  most  frequently  mentioned  contra- 
indication to  the  administration  of  mercury,  and  certainly  when  the 
nephritis  is  not  directly  due  to  syphilis  mercury  should  be  given  with 
the  greatest  care  and  its  action  on  the  kidneys  most  carefully 
watched. 


SPECIFIC  TREATMENT  207 

If,  on  the  other  hand,  the  nephritis  is  due  directly  to  the  syphiUs, 
mercury  will  have  a  beneficial  effect  upon  the  kidney  condition. 
(See  page  293.) 

Malaria. — According  to  Lambkin,^  syphilitics  who  are  suffering 
from  malaria  stand  mercury  badly  and  become  salivated  easily. 
This,  to  the  author's  mind,  applies  only  to  malarial  cachexia,  and 
while  mercury  should  probably  be  withheld  from  syphilitics  during 
the  febrile  stage  of  acute  malaria,  there  is  no  reason  for  so  doing 
as  soon  as  the  paroxysms  are  controlled  by  quinine. 

Physiological  Actions. — There  is  no  doubt  but  that  mercury  in 
small  doses  acts  as  a  tonic,  increasing  the  number  of  red  cells  and 
the  percentage  of  hemoglobin.  But  in  large  doses  mercury  becomes 
a  poison  and  may  cause  many  untoward  symptoms. 

Long  before  the  discovery  of  the  Treponema  pallidum  it  was 
thought  that  the  good  effects  of  mercury  on  syphilis  were  due  to 
its  parasiticidal  effects  upon  the  hypothetical  causative  organism. 
This  has  now  been  abundantly  conJfirmed  both  by  clinical  observa- 
tion on  the  effects  of  mercury  on  the  treponemata  in  syphilitic 
lesions  in  human  beings  and  by  its  effects  on  the  treponemata  in 
experimental  syphilis  in  rabbits.^ 

It  has  also  been  thought  by  some  that  the  beneficial  effects  of 
mercury  are  due  not  to  the  actual  destruction  of  the  infecting  organ- 
ism by  the  mercury  itself,  but  to  the  stimulation  of  the  formation 
of  antibodies.  This  latter  contention  probably  is  not  correct  and 
the  action  of  the  mercury  is  direct  on  the  treponemata. 

The  fate  of  the  mercury  in  the  body  is  of  a  great  deal  of  interest. 
It  has  been  shown  that  no  matter  by  what  method  mercury  is 
administered  some  of  it  remains  in  the  body  tissues  for  a  consider- 
able length  of  time.  This  is  especially  true  of  its  administration 
by  inunction  and  intramuscular  injections.  According  to  Lang,^ 
mercury  was  demonstrated  to  be  in  the  system  in  two  of  his  cases 
three  years  and  in  another  ten  years  after  the  last  course  of  inunction. 

It  has  also  been  shown  that  the  greater  part  of  the  mercury 
administered  is  eliminated  from  the  body  by  the  secretions  and 
excretions.  Thus,  according  to  Lang,^  it  has  been  found  in  the  saliva, 
the  sweat,  the  bile,  the  milk,  the  urine,  and  the  feces,  but  most  in 
the  urine  and  feces.  It  is  sometimes  found  in  the  urine  within  a  few 
hours  after  administration  and  is  eliminated  chiefly  by  the  tubules. 

That  the  mercury  reaches  all  the  tissues  of  the  body  has  been 
demonstrated  by  numerous  investigators.     Lang  states  that  the 

1  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  ii,  p.  302. 

2  Nichols:  Jour.  Exper.  Med.,  1911,  xiv,  p.  196. 

3  Stedman:  Twentieth  Century  Practice  of  Medicine,  New  York,  1899,  xviii, 
p.  326. 

*  Ibid.,  p.  325. 


208  TREATMENT 

greatest  amount  can  be  found  in  the  kidney,  next  in  the  liver;  the 
intestine  and  spleen  contain  large  quantities,  the  thymus  not  so 
much,  while  in  the  bones,  muscles,  brain,  and  lungs  are  found  but 
small  amounts. 

Untoward  Effects. — Scarcely  any  two  individuals  react  alike  to 
the  effects  of  mercury,  so  it  is  most  essential  with  the  use  of  this 
drug  to  be  on  the  lookout  for  untoward  effects.  The  chief  of  these 
are  salivation,  nephritis,  gastro-intestinal  disturbances,  cutaneous 
eruptions,  and  malnutrition  and  is  eliminated  chiefly  in  the  tubules. 

Salivation,  once  the  bugbear  of  the  use  of  mercury,  is  rarely  seen 
nowadays  in  the  severe  types  formerly  encountered.  At  one  time 
it  was  not  rare  to  see  marked  inflammation  of  the  mucous  membrane 
of  the  mouth  with  ulcerations,  bone  necrosis  of  the  jaw  and  loss 
of  teeth,  while  a  copious  flow  of  ropy  saliva  continuously  drooled 
from  between  the  swollen  lips. 

A  mild  type  of  salivation  not  infrequently  is  seen  and  this  to  the 
author's  mind  is  a  condition  not  to  be  deplored. 

The  first  symptom  of  salivation  is  usually  a  metallic  or  coppery 
taste  in  the  mouth,  although  the  actual  increase  in  the  flow  of 
saliva  may  be  noted  first.  There  is  a  disagreeable  odor  to  the  breath, 
while  the  gums  are  found  to  be  congested  and  bleed  easily.  Upon 
"clicking"  the  teeth  together  they  are  found  to  be  sore,  and  the 
tongue  is  swollen  and  edematous,  showing  the  marks  of  the  teeth 
upon  its  surface.  Ulceration,  especially  behind  the  lower  incisors, 
and  back  of  the  third  lower  molars  also  sometimes  is  seen.  Between 
this  mild  type  of  salivation  and  the  severe  type  described  above 
are  found  all  degrees  of  severity. 

The  treatment  of  mild  salivation  consists  of  withdrawing  the 
mercury,  touching  any  ulcerations  with  an  antiseptic  solution, 
such  as  a  solution  of  equal  parts  of  tincture  of  myrrh  and  tincture 
of  iodin,  and  washing  the  mouth  several  times  daily  with  a  potassium 
chlorate  solution. 

If  in  spite  of  all  precautions  severe  stomatitis  should  occur,  the 
patient  should  be  placed  in  bed  on  a  milk  diet  and  saline  laxatives 
and  diuretics  given.  Diaphoresis  should  be  stimulated  by  wrap- 
ping the  patient  in  blankets  and  surrounding  him  with  hot-water 
bottles.    Or,  if  possible,  hot-air  baths  should  be  administered. 

Potassium  chlorate  internally  has  been  recommended  very  highly, 
but  its  value  probably  has  been  overestimated.  However,  it  cer- 
tainly does  no  harm  and  may  be  administered  in  0.3  gram  (5  grain) 
doses  in  solution  every  two  or  three  hours. 

The  mouth  and  gums  should  be  swabbed  frequently  with  hydrogen 
peroxide  or  some  astringent. 

Nephritis. — It  has  long  been  recognized  that  nephritis  occasionally 
is  seen  during  or  following  the  administration  of  mercury,  so  it  is 


SPECIFIC   TREATMENT  209 

of  the  utmost  importance  that  the  urine  be  examined  frequently 
for  evidence  of  renal  irritation.  Should  mercurial  nephritis  occur 
the  mercury  should  be  withdrawn  and  the  patient  purged  and 
sweated  freely.  After  the  urine  has  returned  to  normal  the  mercury 
may  be  resumed  in  carefully  guarded  doses. 

G astro-intestinal  Disturbances. — Indigestion,  loss  of  appetite, 
more  or  less  severe  pains  in  the  abdomen,  and  diarrhea  not  infre- 
quently accompany  the  ingestion  of  mercury. 

The  administration  of  mercury  by  mouth  as  well  as  by  other 
methods  is  rarely  accompanied  by  more  severe  symptoms  of  enter- 
itis; severe  griping  pains,  bloody,  mucoid  stools,  tenesmus,  etc., 
while  even  death  has  been  observed.  As  a  rule  these  symptoms 
are  observed  with  severe  salivation,  but  may  occur  alone  and  with 
no  warning.  Mild  gastro-intestinal  symptoms  generally  will  abate 
upon  the  withdrawal  of  the  mercury.  If  the  drug  is  being  admin- 
istered by  mouth,  it  usually  can  be  resiuned  by  some  other  method 
with  impunity.  In  the  severe  types  of  enteritis  caused  by  mercury 
it  is  needless  to  say  the  drug  should  be  discontinued  at  once.  Castor 
oil  should  be  administered  and  morphin  hypodermically  to  control 
the  pain.  The  castor  oil  should  be  followed  by  bismuth  and  perhaps 
Dover's  powders.    The  diet  should  be  liquid  but  without  milk. 

Cutaneous  Eruptions. — The  administration  of  mercury  by  inunc- 
tion is  not  infrequently  accompanied  by  more  or  less  severe  der- 
matitis, due  to  the  irritating  action  of  the  mercurial  ointment. 
These  irritative  conditions  are  found  most  frequently  in  individuals 
with  sensitive  skins  or  when  the  inunctions  are  applied  in  hairy 
regions. 

Aside  from  these  conditions  directly  due  to  the  local  action  of 
the  mercury,  certain  other  cutaneous  eruptions  rarely  are  noticed. 
These  latter  are  due  to  the  systemic  effect  of  the  mercury  and  occur 
as  oval  erythematous  patches,  sometimes  elevated  and  resembling 
urticaria.  Minute  purpuric  spots  are  seen  between  the  erythema- 
tous patches,  especially  on  the  legs.  Sometimes  the  eruption  is  of 
a  marked  red  color.  There  is  always  burning  and  pruritus,  and 
usually  more  or  less  fever  and  anorexia  with  general  depression. 
As  a  rule  the  eruption  subsides  promptly  with  desquamation  upon 
the  withdrawel  of  the  mercury. 

Soothing  lotions  should  be  applied  and  cathartics  administered. 
Mercury  should  be  resmned  with  great  care  and  in  small  doses. 

Malnutrition. — During  a  vigorous  course  of  mercurial  treatment, 
occasionally  it  is  found  that  the  patient  is  losing  weight  and 
beconiing  anemic.  This,  however,  as  a  rule,  occurs  only  after  a 
considerable  quantity  of  mercury  has  been  administered,  and  is 
usually  indicative  of  an  approaching  stomatitis. 

That  death  rarely  follows  the  use  of  mercury  in  the  treatment  of 
14 


210  TREATMENT 

syphilis  is  well  known.  Wolffenstein,i  \^  1913^  found  records  in  the 
literature  since  1883  of  108  fatalities.  Only  1  death  resulted  from 
the  internal  administration  of  mercury.  In  this  case  the  patient 
died  following  the  ingestion  of  five  pills  of  0.06  gram  each.  One 
death  followed  the  inhalation  of  mercury  fumes  by  Walander's 
method.  Nine  fatalities  followed  the  use  of  mercurial  oil  {Merkur- 
iolol)  and  10  the  use  of  mercuric  salicylate.  One  of  the  latter  cases 
undoubtedly  exhibited  an  absolute  idiosyncrasy,  as  a  single  injec- 
tion of  0.05  gram  proved  fatal.  Seven  deaths  followed  the  injection 
of  the  soluble  preparations,  78  the  insoluble,  31  of  the  latter  occurred 
following  the  use  of  gray  oil,  while  19  fatalities  resulted  from  the 
use  of  inunctions. 

Comparative  Value  of  Methods  of  Administering  Mercury. — Mouth. — 
The  advantages  of  the  administration  of  mercury  by  mouth  are 
that  it  is  the  easiest  method,  both  for  the  physician  and  the  patient, 
and  that  this  method  can  be  carried  out  at  a  distance  from  the 
physician  with  only  occasional  visits  to  the  latter.  It,  however, 
has  the  following  decided  disadvantages:  it  is  the  least  efficient 
of  the  ordinary  methods  of  administering  mercury;  it  is  more  liable 
to  cause  gastro-intestinal  disturbances  than  other  methods;  and 
finally,  even  the  most  intelligent  patients  and  those  with  the  best 
intentions  not  infrequently  fail  to  follow  instructions  to  the  letter, 
and  more  or  less  often  neglect  to  take  their  medicine. 

Inunctions. — The  only  advantages  of  the  inunction  method  of 
administering  mercury  are  that  it  usually  is  efficient  in  its  action 
and  that  the  mercury  can  be  administered  by  the  patient  himself. 
However,  the  disadvantages  are  so  many  that,  except  in  rare 
instances  the  author  does  not  employ  this  method. 

The  inunction  method  is  inexact,  as  it  is  never  possible  to  deter- 
mine the  amount  of  mercury  which  is  being  absorbed;  in  fact,  it 
has  been  demonstrated  that  it  may  not  be  absorbed  at  all.  Power^ 
states  that  a  patient  was  exhibited  by  Ehrmann  at  the  Dermatolog- 
ical  Congress  at  Vienna  in  1901  in  whose  urine  mercury  could 
not  be  demonstrated  in  spite  of  the  fact  that  he  had  received  twenty 
inunctions  of  mercurial  ointment.  At  the  same  meeting  another 
patient  was  shown  by  Mracek  with  an  extensive  maculopapular 
syphiloderm  who  had  received  400  inunctions  while  mercury  was 
absent  from  the  urine  and  the  eruption  had  actually  increased 
during  the  treatment. 

Further  disadvantages  of  the  inunction  method  are  that  it  is 
dirty  and  disgusting  to  many  patients,  its  administration  usually 
cannot  be  kept  secret,  it  requires  considerable  time,  and  it  may 
cause  dermatitis. 

1  Berl.  klin.  Wchnschr.,  1913,  1,  p.  1925. 

2  System  of  Syphilis,  London,  1909,  ii,  p.  214. 


SPECIFIC  TREATMENT  211 

Fumigation. — The  administration  of  mercury  by  fumigation  is 
little  used,  owing  to  the  trouble  it  incurs,  although  it  is  fairly 
efficacious  (fully  as  much  so  as  the  inunction  method),  is  less  dirty 
than  inunctions  and  less  painful  than  injections. 

Intramuscular. — -The  ease  of  the  intramuscular  injections  of  mer- 
cury, the  exactness  of  the  dose,  and  the  great  efficiency  of  the  drug 
administered  in  this  manner  makes  it  the  method  of  choice  in  nearly 
all  cases  of  syphilis.  It  has  the  further  advantage  of  requiring  more 
or  less  frequent  visits  of  the  patient  to  the  physician.  The  only 
disadvantage  is  the  pain  which  occurs  in  some  individuals  in  spite 
of  all  precautions.  But,  as  a  rule,  the  pain  is  so  slight  that  it  is 
willingly  borne  by  the  vast  majority  of  patients. 

In  such  patients  who  cannot,  or  will  not,  stand  the  pain  it  is, 
of  course,  necessary  to  resort  to  other  methods  of  administration. 
In  such  instances  the  author  usually  employs  the  intravenous 
method  or  rarely  the  inunction  method. 

The  relative  merits  of  the  various  soluble  and  insoluble  prepara- 
tions of  mercury  used  intramuscularly  have  been  discussed  above. 

Intravenous. — The  only  advantages  of  the  intravenous  adminis- 
tration of  mercury  are  its  direct  introduction  into  the  blood  stream, 
thus  giving  it  a  more  rapid  action  and  the  comparative  freedom 
from  pain.  The  disadvantages  are  the  difficulty  of  technic  and  the 
phlebitis  and  periphlebitis  which  sometimes  follow,  except  when 
mercurialized  serum  or  the  method  of  Nixon  is  employed.  However, 
it  is  to  be  recommended  highly  in  severe  cases  where  quick  results  are 
wanted  and  in  patients  who  complain  of  much  pain  on  intramuscular 
injections. 

Suiypositories. — This  method  of  administering  mercury  has 
received  but  slight  notice  in  this  country,  although  Audry  considers 
it  as  efficient  as  the  ingestion  method  and  open  to  no  objections. 

Arsenic. — Herzfeld^  states  that  according  to  Harles  the  use  of 
arsenic  in  the  treatment  of  syphilis  dates  as  far  back  as  the  time  of 
Fallopius  and  Libavius,  and  that  in  the  middle  of  the  eighteenth 
century  Hoffmann  employed  the  "fiores  auri  pigmenti  diaphoretici" 
in  the  treatment  of  "  lues  venerea  inveterata"  in  cases  which  resisted 
mercurial  treatment  and  also  in  cases  in  which  ptyalism  and  mer- 
curial poisoning  developed. 

Herzfeld  further  quotes  Ziegenbuehler  as  having  used  arsenic 
internally  successfully  for  the  treatment  of  syphilitic  arthritis  in 
1809,  while  Horn  and  Renner  are  said  to  have  employed  white 
arsenic  with  success  in  old  inveterate  syphilitic  lesions. 

After  the  introduction  of  the  hypodermic  needle  this  method 
was  employed  for  the  administration  of  arsenic.     The  most  fre- 

1  Jour.  Am.  Med.  Assn.,  1911,  Ivi,  p.  588. 


212  TREATMENT 

quently  used  preparations  were  the  liquor  potassii  arsenitis  (Fowler's 
solution)  and  the  liquor  sodii  arsenitis  Pearson  (Pearson's  solu- 
tion). On  account  of  the  irritating  action  of  these  solutions  which 
sometimes  caused  them  to  produce  abscesses,  or  even  gangrene, 
Ziemssen^  was  led  to  employ  a  1  per  cent,  solution  of  sodium 
arsenite.  This  solution  also,  according  to  Herzfeld,^  proved  irri- 
tating and  painful.  The  latter  author  therefore  prepared  an 
arsenical  solution  for  hypodermic  injection  as  follows: 

One  gram  of  arsenous  acid  and  2.25  c.c.  of  normal  soda  solution 
are  added  to  100  c.c.  of  distilled  water  and  boiled  until  the  solution 
is  clear.  It  is  then  filtered  and  made  up  to  100  grams  with  distilled 
water. 

The  initial  dose  recommended  is  0.25  c.c.  which  is  to  be  increased 
gradually  to  1  c.c.  or  even  2  c.c.  No  untoward  results  except  a 
slight  burning  were  observed. 

In  1911  Herzfeld^  reported  the  cure  of  two  cases  of  syphilis,  both 
of  which  had  resisted  active  treatment  with  mercury,  one  for  six 
months  and  the  other  for  five  years,  by  fourteen  and  twenty-four 
injections,  respectively,  of  his  solution. 

About  this  time  numerous  investigators  reported  on  the  use  of 
the  organic  compounds  of  arsenic  in  the  treatment  of  syphilis. 

Atoxyl  or  Sainine. — Atoxyl  or  samine,  as  it  is  sometimes  called, 
was  one  of  the  first  of  these  compounds  to  be  employed.  Chemically 
this  drug  is  para-amidopheyiyl-sodiitm  arsenate,  and  has  the  follow- 
ing structural  formula: 

0-H 
/ 

As— O 

\ 
0-Na 

/ 
C 

/     \ 
H-C  C-H 

H-C  C-H 

\     / 
C 

H-  N  -H 

It  is  a  white  crystalline  powder  and  has  been  used  both  internally 
and  hypodermically.  Metchnikoff  found  that  atoxyl  was  quite 
valuable  both  in  treatment  and  as  a  prophylactic  measure  in  experi- 
mental syphilis.  It  was  therefore  tried  in  human  syphilis  by 
Lambkin,  Uhlenhuth  and  Manteufel  and  others  in  doses  of  0.2  to 

1  Deutsch.  Arch.  f.  klin.  med.,  1889,  Ivi,  p.  124. 

2  .Jour.  Am.  Med.  Assn.,  1909,  lii,  p.  557. 

3  Ibid.,  1911,  hd,  p.  588. 


SPECIFIC   TREATMENT  213 

0.6  gram  (3  to  10  grains) .  It  was  soon  found,  however,  that  while 
atoxyl  was  very  effective  in  the  treatment  of  certain  cases  of  syphilis, 
especially  those  that  were  resistant  to  mercury,  its  toxic  qualities 
occasionally  were  so  great  that  its  use  was  attended  with  consider- 
able danger.  Even  in  minute  doses  sometimes  it  was  found  to  cause 
nephritis,  gastro-intestinal  disturbance,  and  even  blindness.  A 
bright  rose-colored  rash  also  not  infrequently  is  observed  following 
the  use  of  this  drug. 

Soamin. — Soamin  is  the  trade  name  for  a  similar  preparation 
which  is  said  by  its  manufacturers  to  be  much  less  toxic  than  atoxyl. 
This  drug  has  had  considerable  vogue  both  in  England  and  America 
as  a  specific  for  syphilis,  but  upon  the  introduction  of  salvarsan 
largely  fell  into  disuse. 

Sodium  Cacodylate. — Sodium  cacodylate,  which  has  been  known 
for  many  years,  probably  has  been  used  in  this  country  more  than 
any  of  the  other  compounds  of  arsenic  in  the  treatment  of  syphilis, 
with  the  exception  of  the  Ehrlich  preparations.  Chemically  sodium 
cacodylate  is  dimethyl-sodium-ar senate,  and  has  the  following  for- 
mula: (CH3)2  AsO.ONa  +  3H2O.  It  is  a  white  amorphous  powder, 
soluble  in  water  and  usually  is  used  in  doses  of  from  0.03  to  0.3 
gram  (|  to  5  grains)  by  mouth,  intramuscularly  or  intravenously. 

One  of  the  earliest  and  most  enthusiastic  advocates  of  sodium 
cacodylate  in  the  treatment  of  syphilis  was  Murphy^  and  even  in 
spite  of  the  wide-spread  use  of  salvarsan  as  late  as  October,  1914, 
had  the  following  to  say  concerning  the  use  of  the  former  drug:^ 
"We  have  two  very  interesting  cases  that  came  into  the  office 
yesterday.  The  first  is  that  of  an  engineer  who  contracted  a  chancre 
of  the  tongue  at  its  middle  from  smoking  a  pipe  that  had  been  used 
by  his  syphilitic  fireman.  At  the  time  of  his  first  visit  eight  days 
previously  we  immediately  scraped  his  tongue,  excised  a  piece, 
and  stained  for  spirochetes,  the  detection  of  which  confirmed  the 
diagnosis.  Then  we  instituted  what  we  believe  to  be  the  best 
method  of  treating  early  syphilis,  namely,  daily  hypodermic  injec- 
tions of  sodium  cacodylate.  I  recently  recommended  salvarsan,  but 
I  have  returned  to  sodium  cacodylate,  which  I  originally  suggested 
and  used  before  we  had  "606."  Upon  his  return  yesterday  the 
chancre  was  shrunken  to  one-sixth  its  original  size.  I  know  that 
it  will  be  healed  when  he  returns  for  the  next  visit,  six  days  hence, 
allowing  just  two  weeks  from  the  time  of  the  original  sodium  caco- 
dylate injection  to  that  of  complete  healing.  Usually  chancres 
heal  within  from  six  to  seven  days  and  much  faster  with  sodium 
cacodylate  than  with  salvarsan.  As  to  the  permanency  of  the  cure 
we  are  not  so  certain,  but  we  do  know  that  "  606"  has  been  a  failure, 

1  Jour.  Am.  Med.  Assn.,  1910,  Iv,  p.  1113. 

2  Clinics  of  John  B.  Murphy,  M.D.,  1915,  iv,  p.  574. 


214  TREATMENT 

as  regards  permanency  of  cure,  and  a  great  disappointment.  I 
give  the  sodium  cacodylate  immediately  after  the  appearance  of 
the  initial  lesion,  and  keep  it  up  until  the  external  manifestations 
have  entirely  disappeared — two  weeks,  three  weeks,  four  weeks. 
First  we  commence  with  2  grains  once  a  week,  always  starting  with 
the  smaller  doses.  Why?  Because  some  patients  have  an  idiosyn- 
crasy to  arsenic.  This  has  been  known  as  long  as  arsenic  has  been 
known.  If  the  idiosyncrasy  is  marked,  it  gives  the  patient  the  garlic 
breath.  If  there  is  no  idiosyncrasy,  the  sodium  cacodylate  is  pushed 
up  to  5  grains." 

Other  investigators,  however,  have  not  been  so  enthusiastic  over 
the  use  of  sodium  cacodylate.  Long^  reported  the  injection  of  this 
drug  in  4  cases,  3  of  "secondary",  and  1  of  "tertiary"  syphilis  in  which 
it  was  useless,  in  fact  harmful,  as  all  of  the  patients  suffered  relapses 
under  its  use. 

The  injection  of  sodium  cacodylate  intravenously  has  been  prac- 
tised by  several  workers,  the  average  dose  being  0.32  gram  (5  grains) , 
although  as  much  as  1  gram  (15  grains)  has  been  injected  at  one  dose 
without  any  untoward  effects.^ 

,  The  author  recently  has  used  this  method  in  several  cases  with 
apparently  favorable  results.  It  has,  however,  been  employed  with 
mercury,  so  definite  conclusions  cannot  be  drawn.  The  drug  as 
placed  upon  the  market  in  sterilized  ampules  is  used,  is  diluted 
to  10  to  20  c.c.  with  normal  salt  solution,  and  injected  in  a  similar 
manner  to  neosalvarsan.     (See  page  229.) 

A  solution  of  sodium  cacodylate  has  been  placed  upon  the  market 
in  this  country  under  the  trade  name  of  "  Venarsen,"  and  has  been 
advertised  most  extensively.  This  compound,  according  to  the 
label  appearing  on  the  wrapper,  is  a  "comparatively  non-toxic  organic 
arsenic  compound,  0.7  gm.,  representing  288  mgs.  (4.37  grains)  of 
metallic  arsenic  and  0.78  mg.  {-jf-Q  grain)  metallic  mercury  in 
chemical  combination." 

The  report  of  the  Council  on  Pharmacy  and  Chemistry  of  the 
American  Medical  Association^  states  that  Venarsen  is  a  simple 
solution  containing  approximately  9  grains  of  sodium  cacodylate, 
4^  grain  of  mercury  biniodide,  and  f  grain  of  sodium  iodide  to 
each  full  dose 

It  was  rejected  by  the  Council  on  the  grounds  of  unwarranted 
therapeutic  claims,  poisonous  ingredients  not  stated  on  the  label 
(this  objection  has  now  been  removed) ,  the  name  does  not  express 
the  chemical  composition,  and  unscientific  combination.  There  is 
no  doubt  that  the  intravenous  injection  of  sodium  cacodylate  and 

1  Jour.  Am.  Med.  Assn.,  1911,  Ivii  p.  23. 
^  Stukes:  Jour.  Med.  Assn.  Georgia,  1914. 
3  Jour.  Am.  Med.  Assn.,  1915,  Ixv,  p.  1780. 


SPECIFIC   TREATMENT  215 

mercury  in  syphilis  is  of  benefit,  but  if  the  physician  wants  to  use 
these  drugs  in  this  manner  it  would  be  far  better  to  prepare  them 
himself  after  the  methods  described  above,  as  by  so  doing  he  can 
gauge  accurately  the  dose  of  each  and  know  the  purity  of  his  prepa- 
rations. Further,  the  cost  of  Venarsen  as  marketed  is  very  much 
greater  than  the  cost  of  the  drugs  if  prepared  by  the  physician. 

Salvarsan. — History. — Probably  no  other  therapeutic  agent  in  all 
the  history  of  medicine  created  the  furor  that  did  the  introduction 
of  this  arsenical  compound,  and  probably  no  other  drug  has  been 
so  widely  praised  or  so  widely  condemned. 

Salvarsan  was  not  the  result  of  an  accident.  It  was  the  outcome 
of  many  painstaking  experiments,  and  was  built  up  step  by  step 
with  the  ultimate  goal  in  view  of  finding  the  ideal  remedy  for  syphilis. 
Its  production  and  its  underlying  principle  place  the  name  of 
Ehrlich  by  the  side  of  those  of  John  Hunter  and  Lord  Lister  as 
among  the  greatest  medical  men  of  all  time.  Ehrlich  approached  the 
problem  from  an  entirely  new  stand-point.  From  the  very  beginning 
of  his  experimental  work  this  great  scientist  was  imbued  with  the 
idea  that  a  specific  chemical  affinity  exists  between  specific  living 
cells  and  specific  chemicals.  This  idea  is  seen  in  his  work  with 
the  leukocytes,  and  in  his  vital  staining  experiments.  From  this 
basic  idea  it  was  an  easy  step  to  the  theory  that  for  each  parasite 
a  specific  curative  drug  could  be  found,  and  Ehrlich's  aim  was  to 
produce  a  drug  which  would  completely  destroy  all  of  the  specific 
parasites  in  a  given  body  with  one  injection. 

The  term  "tropism"  was  used  to  designate  the  relations  of  the 
chemical  compounds  to  the  organs  of  the  host  as  well  as  to  the 
parasites,  and  the  complete  destruction  of  the  parasites  with  one 
injection  was  termed  "therapia  magna  sterilisma." 

His  first  work  along  this  line  was  with  the  trypanosome  of  sleep- 
ing sickness  in  mice,  and  in  a  short  time  a  new  dye,  trypan-red, 
was  produced  which  completely  sterilized  the  body  of  the  mouse 
with  one  injection. 

Atoxyl  was  next  employed  and  from  this  by  changing  the  amido 
group  a  very  large  number  of  preparations  were  produced  and 
tested.  The  object  was  to  find  the  compound  which  would  produce 
a  maximum  parasiticidal  effect  (maximum  parasitotropism) ,  with  a 
minimum  toxic  eft'ect  on  the  organism  (minivium  organotropism) . 

It  was  soon  demonstrated  that  arsenic  in  its  trivalent  state  was 
much  more  effective  on  trypanosomes  than  in  its  pentavalent  state, 
and  of  hundreds  of  compounds  produced  and  experimented  with 
only  a  few  were  found  to  be  at  all  suitable.  The  principal  ones  of 
these  are  arsacetin,  arsenophenylglycin,  arsanilate  of  mercury,  and 
finally  dioxydiamidoarsenobenzol  or  salvarsan.  This  now  famous 
remedy  was  the  six  hundred  and  sixth  compound  tried,  and  has 


216 


TREATMENT 


therefore  popularly  been  known  as  "606."  Wechselmann^  quotes 
Hata,  who  conducted  the  animal  experiments  for  Ehrlich,  concerning 
the  action  of  the  above-mentioned  compounds  on  chicken  spiril- 
losis,  as  follows: 

liESTTLTS    OF    TREATMENT   FOR    ChICKEN    SpIRILLOSIS. 


Infection  intramuscular. 

Treatment  two  days  after  infection;  also  intramuscular. 

Remedy. 

Dosis  tolerata 
per  kilo. 

Dosis  curativa 
per  kilo. 

C 

T 

Atoxyl 

Arsacetin 

Arsenophenylglycin     .... 
Arsanilate  of  mercury 
Salvarsan 

0.06  gm. 
0.1     gm. 
0.4    gm. 
0.1     gm. 
0.2    gm. 

0.03       gm. 
0.03       gm. 
0.12       gm. 
0.04       gm. 
0.0035  gm. 

1.0 

i.o 

tV.o 

"This  comparison  clearly  shows  that  the  results  with  the  first  four 
remedies  are  far  less  satisfactory  than  that  with  the  salvarsan,  in 
which  the  ratio  ^  is  actually  ideal." 

Later  the  new  remedy  was  tried  on  experimental  syphilis  in  rab- 
bits, and  it  was  found  that  one  intravenous  injection  of  salvarsan 
in  doses  of  0.015  to  0.04  gram  would  cause  the  disappearance  of 
the  treponemata  from  chancres  of  the  scrotum  within  twenty-four 
hours  and  a  complete  cure  resulted  in  from  two  to  three  weeks. 
Smaller  doses  0.0075  to  0.005  gram  caused  the  treponemata  to 
vanish  in  from  two  to  three  days,  while  complete  cure  followed  in 
from  two  to  four  weeks.  Smaller  doses  failed  to  cause  the  disap- 
pearance of  the  organisms. 

The  first  use  of  salvarsan  in  human  beings  was  the  injection  of 
two  physicians  who  volunteered  for  the  experiment,  and  no 
untoward  effects  were  noted  except  pain  and  swelling  at  the  site 
of  innoculation.  It  was  then  employed  in  twenty-three  cases, 
mostly  paretics,  in  Alt's^  clinic.  The  dose  used  was  0.3  gram. 
Alt  then  requested  Schreiber,  of  the  Altstaditische  Krankenhaus 
in  Magdelburg,  to  try  the  new  drug  in  recent  cases  of  syphilis. 
This  was  done  with  twenty-seven  patients  suffering  from  various 
syphilitic  manifestations,  with  some  most  startling  results. 

On  February  18,  1910,  Ehrlich  turned  over  a  quantity  of  salvarsan 
to  Wechselmann^  for  further  and  more  extensive  experiments. 
It  was  to  be  used  in  doses  of  at  least  0.3  gram,  and  only  in  syphili- 
tics  otherwise  healthy  but  who  had  not  been  treated  with  mercury. 

1  The  Treatment  of  Syphilis  by  Salvarsan,  New  York  and  London,  1911,  p.  12. 

2  Miinchen.  med.  Wchnschr.,  1910,  Ivii,  p.  561. 

3  The  Treatment  of  Syphilis  with  Salvarsan,  New  York  and  London,  1911,  p.  19. 


SPECIFIC  TREATMENT  217 

The  first  results  of  his  work  were  reported  by  Wechselmann^  before 
the  Berlin  Medical  Society  June  22,  1910. 

Other  investigators,  including  Neisser,^  Schreiber  and  Hoppe,'^ 
Fischer  and  Hoppe,*  Loeb,'^  and  Treupel,*'  were  entrusted  with 
salvarsan  and  reported  upon  its  use. 

The  new  preparation  was  received  in  America  early  in  May,  1910, 
and  soon  several  reports  concerning  its  use  appeared.  Among  the 
first  American  physicians  to  use  salvarsan  may  be  mentioned  Nichols 
and  Fordyce,^  Eisner,^  Engmann,  Mook  and  Marchildon,^  and  Fox.^" 

Early  in  1911  the  drug  was  placed  upon  the  market  in  this  coun- 
try, and  soon  an  enormous  literature  sprang  up  concerning  it. 

Salvarsan  is  a  patented  preparation,  and  for  a  long  time  was 
manufactured  exclusively  by  Farbwerke  vorm.  Meister  Lucius  and 
Bruning,  Hoechst  O.M.,  but  since  the  beginning  of  the  great 
European  war  has  been  prepared  in  England  under  the  name  of 
Kharsivan,  in  France  under  the  name  of  Arsenohensol- Billon, 
and  in  Canada  under  the  name  of  diarsenol.  It  has  also  been  pre- 
pared in  this  country  by  Schamberg  and  his  associates,^^  and  is 
termed  arsenohenzol.  The  author  has  used  over  200  doses  of  this 
latter  preparation  and  finds  it  apparently  identical  with  the  German 
product,  except,  perhaps,  slightly  less  soluble.  The  therapeutic 
effects  are  equally  as  good. 

Physical  and  Chemical  Properties. — Salvarsan  is  a  yellowish, 
crystalline,  hydroscopic  powder,  containing,  according  to  its  manu- 
facturers, about  34  per  cent,  of  arsenic.  The  chemical  name  is 
dioxydiamidoarsenobenzol  dihydrochloride,  and  the  structural 
formula  is  as  follows: 

As  ==As 

C  .  C 

/     \  /     \ 

H— C  C— H  H— C  C— H 

CIHNH2— C  C— H  H— C  C— NH2CIH 

\     /  \     / 

c  c 

OH  OH 

It  is  very  unstable  in  air  and  therefore  is  sealed  in  vacuum  tubes. 
Upon  the  addition  of  water  a  sticky,  gelatin-like  mass  is  formed 

1  B'erl.  klin.  Wchnschr.,  1910,  xlvii,  p.  1261. 

2  Deutsch.  med.  Wchnschr.,  1910,  xxxvi,  p.  1212. 

3  Miinchen.  med.  Wchnschr.,  1910,  Ivii,  p.  1430. 

^  Ibid.,  p.  1531.  6  Ibid.,  p.  1580. 

^  Deutsch.  med.  Wchnschr.,  1910,  xxxvi,  p.  1393. 

7  Jour.  Am.  Med.  Assn.,  1910,  Iv,  p.  1171. 

8  Ibid.,  p.  2052.  s  Ibid.,   1911,  Ivi,  p.  87. 

i»  Ibid.,  p.  650.  11  Ibid.,  1915,  Ixv,  p.  1387. 


218  TREATMENT 

which  readily  dissolves  in  an  excess  of  water,  especially  if  hot.  The 
solution  formed  is  a  clear  yellow  color  of  a  depth  depending  upon 
the  amount  of  water  and  of  a  distinct  acid  reaction.  The  addition 
of  sodium  hydroxide  causes  a  precipitate  to  be  formed  which  redis- 
solves  upon  the  further  addition  of  the  alkali. 

According  to  Puckner  and  Hilpert^  the  reaction  which  takes 
place  apparently  consists  in  the  liberation  of  the  water  insoluble 
free  base:  thus,  HCl.NHa.OH.CeHg.As:  As.CeHg.OH.NHa.HCl 
+  2NaOH— >  NHa.OH.CeHg.As:  As.C6H3.OH.NH2  +  2NaCl  + 
2H2O,  the  phenolic  hydroxyl  of  which  then  reacts  with  the  alkali 
to  form  the  water  soluble  sodium  salt  (the  phenolate  of  the  base) ; 
thus,  NH2OH.C6H3.As:  As.C6H3.0H.NH2  +  2NaOH.— >NH20Na. 
C6H3.AS:  As.C6H3.ONa.NH2  +  2H2O 

The  addition  of  a  solution  of  sodium  carbonate  to  an  aqueous 
solution  of  salvarsan  also  causes  a  precipitate  which,  however, 
does  not  dissolve  upon  the  addition  of  a  further  quantity  of  the 
alkali  carbonate. 

The  aqueous  solution  of  salvarsan  is  not  affected  by  the  addition 
of  weak  nitric,  hydrochloric,  or  sulphuric  acids.  Strong  nitric  acid, 
however,  causes  a  yellowish-white  precipitate  which  redissolves 
upon  the  addition  of  more  acid,  leaving  a  dark  red  solution.  A 
yellowish-white  precipitate  also  is  formed  upon  the  addition  of 
strong  sulphuric  acid.  This  is  redissolved  when  more  acid  is 
added  and  an  almost  colorless  solution  remains  which  becomes 
brown  and  finally  black,  apparently  through  carbonization.  Ferric 
chloride  added  to  an  aqueous  solution  of  salvarsan  produces  a 
violet  coloration,  similar  to  many  other  phenols,  which,  upon  stand- 
ing, becomes  dark  red  and  finally  turbid. 

A  solution  of  salvarsan  treated  with  diluted  nitric  acid  and  then 
silver  nitrate  develops  a  yellow  precipitate  which  rapidly  darkens 
and  soon  becomes  black. 

An  alkaline  solution  of  potassium  permanganate  added  to  the 
salvarsan  solution  and  warmed  is  reduced  and  an  odor  of  ammonia 
observed.  The  addition  of  y^  iodin  solution  to  a  solution  of  sal- 
varsan causes  the  gradual  disappearance  of  the  iodin  color  as 
well  as  the  yellow  color  of  the  salvarsan  until  a  colorless  liquid  is 
obtained.  This  appears  to  be  a  perfectly  definite  reaction,  0.0651 
gram  of  the  salvarsan  requiring  10.5  c.c.  y^  iodin  solution,  regard- 
less of  the  dilution. 

Methods  of  Administration. — Salvarsan  has  been  injected  into 
the  body,  subcutaneously,  intramuscularly,  and  intravenously, 
although  the  latter  method  has  superseded  the  two  other  methods 
almost  altogether  with  the  majority  of  workers.     Salvarsan  has 

1  Jour.  Am.  Med.  Assn.,  1910,  Iv,  p.  2134, 


SPECIFIC  TREATMENT  219 

also  been  administered  by  mouth  and  by  enteroclysis.  It  goes 
without  saying  that  all  apparatus  used  in  the  preparation  and 
injection  of  salvarsan,  whether  the  subcutaneous,  the  intramus- 
cular, or  the  intravenous  method  is  employed,  should  be  sterilized 
thoroughly,  preferably  by  autoclave,  and  all  manipulations  should 
be  carried  out  with  scrupulous  aseptic  technic. 

Subcutaneous  and  Intramuscular  Injection. — Salvarsan  may  be 
administered  by  subcutaneous  or  intramuscular  injection  either 
in  simple  acid  solution,  in  alkaline  solution,  in  neutral  suspension, 
or  in  oily  or  paraffin  suspension. 

Acid  Solution. — Salvarsan  is  prepared  for  injection  in  acid  solu- 
tion by  simply  dissolving  in  a  sufficient  quantity  of  hot  sterile 
distilled  water  to  make  a  10  per  cent,  solution.  The  local  reaction 
following  either  the  subcutaneous  or  intramuscular  injection  of 
salvarsan  prepared  by  this  method  usually  is  so  great  that  it  is 
rarely  used  nowadays. 

Alkaline  Solution  (Alt). — Ten  c.c.  of  sterile  distilled  water  are 
placed  in  a  beaker  or  mortar  of  about  50  c.c.  capacity,  the  salvarsan 
added  and  triturated  with  a  glass  rod  or  pestle  until  completely 
dissolved.  Normal  (4  per  cent.)  sodium  hydroxide  solution  is  now 
added  in  the  proportion  of  0.5  c.c.  to  each  0.1  gram  of  the  drug. 
The  stirring  is  continued  until  a  precipitate  is  formed  and  is  par- 
tially redissolved.  The  alkali  solution  is  now  added  drop  by  drop 
until  the  opacity  nearly  clears.  It  is  not  desirable  to  permit  the 
solution  to  become  completely  clear,  as  such  a  solution  is  more 
irritating  to  the  tissues  than  the  slightly  turbid  solution.  The 
total  volume  is  now  made  up  to  20  c.c. 

Alkaline  Solution. — The  following  method  for  preparing  sal- 
varsan for  intramuscular  injection  in  alkaline  solution  is  described 
in  the  wrapper  of  each  ampule  of  the  drug  put  out  by  the  manu- 
facturers : 

The  drug,  for  example  0.5  gram,  is  triturated  in  a  sterile  mortar 
with  0.95  c.c.  (19  drops)  ^  of  15  per  cent,  sodium  hydroxide  solution 
and  diluted  to  the  desired  volume,  usually  5  c.c,  with  sterile 
distilled  water. 

Neutral  Suspensicm  (Wechselmann) . — At  first  Wechselmann^  dis- 
solved the  salvarsan  in  a  small  amount  of  methyl  alcohol  or  glycol, 
added  about  10  c.c.  of  distilled  water,  and  then  1  to  2  c.c.  of  -j-q 
sodium  hydroxide.  To  this  he  then  added  distilled  water  up  to 
25  c.c.  and  injected  the  solution  intragluteally. 

However,  this  investigator  later  adopted  the  following  technic: 
The  salvarsan  is  placed  in  a  mortar  and  dissolved  in  1  or  2  c.c. 
of  15  per  cent,  sodium  hydroxide  solution.    To  this  glacial  acetic 

1  See  table  under  Preparation  for  Intravenous  Injection. 

2  The  Treatment  of  Syphilis  with  Salvarsan,  New  York  and  London,  1911,  p.  73. 


220  TREATMENT 

acid  is  added,  drop  by  drop,  until  "  a  fine  yellow,  shiny  sediment  is 
precipitated,"  when  1  or  2  c.c.  of  sterile  distilled  water  are  added. 
The  reaction  is  determined  by  the  use  of  litmus  paper  and  15  per 
cent,  sodium  hydroxide  or  glacial  acetic  acid  added,  drop  by  drop, 
until  a  neutral  reaction  is  secured.  A  platinum  loop  is  used  to 
transfer  a  drop  of  the  mixture  to  the  litmus  paper.  The  emulsion 
is  now  centrifugalized,  the  supernatent  fluid  pipetted  off  and  dis- 
carded, the  emulsion  taken  up  in  4  to  6  c.c.  of  sterile  distilled  water 
or  salt  solution  and  injected  either  subcutaneously  or  intra- 
muscularly. 

Neutral  Suspension  (Michaelis). — The  salvarsan  is  dissolved  in 
a  solution  prepared  by  adding  0.3  to  0.6  gram  of  sodimn  hydrochlo- 
rate  to  16  c.c.  of  very  hot  sterile  distilled  water  in  a  wide  graduated 
cylinder.  A  glass  rod  may  be  used  as  an  aid  in  dissolving  the  sal- 
varsan. When  this  is  accomplished,  from  3  to  5  c.c.  of  normal 
sodium  hydroxide  solution  are  added  and  the  mixture  thoroughly 
stirred.  Three  drops  of  a  0.5  per  cent,  solution  of  phenolphthalein 
in  70  per  cent,  alcohol  are  added  as  an  indicator,  which  causes  a 
red  color  to  develop.  Then  1  per  cent,  acetic  acid  solution  is  added, 
drop  by  drop,  until  the  red  color  disappears.  The  salvarsan  is 
precipitated  as  fine  yellow  floculi  and  finally  a  few  drops  of  the  nor- 
mal sodium  hydroxide  solution  are  added  to  recolor  slightly  the 
the  phenolphthalein.  The  solution  is  then  ready  for  injection  either 
subcutaneously  or  intramuscularly. 

Oily  and  Paraffine  Emulsions. — Salvarsan  may  be  prepared  for 
subcutaneous  and  intramuscular  injection  by  rubbing  it  up  with 
sterile  olive  oil,  oil  of  sesame,  oil  of  bitter  almond,  liquid  vaselin 
or  liquid  paraffin,  usually  in  the  proportion  of  0.1  gram  to  1  c.c. 

Intravenous  Injection. — Numerous  methods  have  been  described 
for  preparing  salvarsan  for  intravenous  injection.  The  one  most 
frequently  employed,  perhaps,  is  that  described  in  the  wrapper  of 
the  salvarsan  ampule,  and  is  as  follows: 

"  Into  a,  narrow-necked  graduated  glass-stoppered  sterile  cylinder 
measure  of  300  c.c.  capacity,  containing  about  50  sterile  glass  beads, 
30  to  40  c.c.  sterile  distilled  water  is  measured.  Then  the  salvarsan, 
e.  g.,  0.5  gram,  is  added.  With  vigorous  shaking  the  substance 
goes  into  solution.  To  this  solution,  but  only  after  it  has  become 
absolutely  clear  and  no  undissolved  particles  can  be  seen,  19  drops 
of  a  15  per  cent,  caustic  soda  solution  in  accordance  with  the  fore- 
going table  are  added.  This  causes  a  precipitate  to  form,  which 
again  dissolves  on  shaking.  The  clear  yellow  solution  is  now  filled 
up  to  250  c.c.  with  sterile  0.5  per  cent,  saline  solution,  which  is 
prepared  from  chemically  pure  sodium  chloride  and  sterile  freshly 
distilled  water.  Should  the  solution  not  be  quite  clear  or  become 
slightly  turbid  after  a  few  minutes  a  few  more  drops  of  caustic  soda 


SPECIFIC  TREATMENT  221 

solution  should  be  added,  a  drop  at  a  time,  and  waiting  two  or  three 
minutes  after  each  drop  to  see  if  this  quantity  sufRces  to  clear  the 
solution.  Each  50  c.c.  of  this  solution  contains:  0.1  gram  (1^ 
grains)  salvarsan;  consequently  in  100  c.c.  0.2  gram  (3  grains), 
in  150  c.c.  0.3  gram  (4^  grains),  in  200  c.c.  0.4  gram  (6  grains), 
salvarsan." 

The  following  table  is  given  as  a  guide  to  the  amount  of  sodium 
hydroxide  to  use.  for  the  various  doses  of  the  drug : 

Solution  of  Sodium  Hydroxide. 
(Rp.  Purified  Sodium  Hydroxide  1.5  gram.) 

Salvarsan.  Distilled  water.  8.5  c.c. 

0.6  gram  1 .308  gram  =  circa  1 .  14  c.c.  =  circa  23-24  drops 

0.5     "  1.090     "      =     "     0.95  c.c.  =      "     19-20      " 

0.4     "  0.872     "      =     "     0.76  c.c.  =      "     15-16      " 

0.3      "  0.654     "      =      "     0.57c.c.=      "      12 

0.2     "  0.436     "      =     "     0.38  c.c.  =      "       8 

The  manufacturers  insist  that  the .  salvarsan  be  dissolved  in 
distilled  water,  not  in  salt  solution,  that  the  sodium  hydroxide  be 
added  all  at  once,  not  gradually,  that  chemically  pure  sodium  chlo- 
ride be  used  in  preparing  the  saline  solution,  and  finally  that  the 
water  be  freshly  distilled. 

Carter^  advocates  the  intravenous  injection  of  salvarsan  in  con- 
centrated solution  and  prepares  it  as  follows:  The  salvarsan  is 
dissolved  in  from  5  to  10  c.c.  of  sterile  distilled  water,  15  per  cent, 
sodium  hydroxide  solution  is  added  as  outlined  above  and  the  total 
volume  made  up  15  c.c.  with  sterile  distilled  water. 

The  author  for  some  time  has  employed  a  method  which  is  a 
compromise  between  the  use  of  the  usual  highly  diluted  solution 
and  the  concentrated  method.  The  salvarsan  is  placed  in  a  sterile 
glass  graduate  of  100  c.c.  capacity  and  5  to  10  c.c.  of  hot  sterile 
distilled  water  added.  It  is  then  stirred  with  a  sterile  glass  rod 
until  the  salvarsan  is  completely  dissolved.  Fifteen  per  cent, 
sodium  hydroxide  solution  is  added  according  to  the  above  table 
and  the  stirring  continued  until  the  solution  is  perfectly  clear. 
If  necessary  a  few  drops  of  normal  sodium  hydroxide  are  added, 
the  mixture  being  stirred  after  the  addition  of  each  drop.  Normal 
sodium  hydroxide  is  used  here  instead  of  the  15  per  cent,  solution 
to  obviate  the  danger  of  making  the  solution  too  alkaline.  The 
solution  is  now  filtered  through  a  filter  paper  sterilized  in  the  hot- 
air  sterilizer  and  made  up  to  such  a  quantity  with  0.5  per  cent, 
sodium  chloride  solution  that  each  10  c.c.  contains  0.1  gram  of  sal- 
varsan. If  several  patients  are  to  be  treated  in  succession  three 
or  four  doses  may  be  prepared  at  one  time.    Freshly  distilled  water, 

1  South.  Med.  Jour.,  1915,  viii,  p.  882. 


222  TREATMENT 

not  over  six  hours  old,  is  used  in  the  preparation  of  the  salt  solution. 
This  is  distilled  each  morning  into  flasks  which  have  been  sterilized 
in  the  hot-air  sterilizer,  chemically  pure  sodium  chloride  added,  and 
the  solution  autoclaved  for  fifteen  minutes  at  15  pounds  pressure. 
A  flask  of  the  freshly  distilled  water  for  making  the  original  solu- 
tion of  the  salvarsan  is  also  autoclaved. 

Neosalvarsan. — The  great  difficulty  encountered  by  many 
workers  in  preparing  salvarsan  for  injection  lead  Ehrlich  to  seek  a 
substance  of  equal  potency  but  requiring  a  less  complicated  technic 
in  preparation.  On  his  914th  experiment  this  was  found,  was  desig- 
nated ''914,"  and  owing  to  its  resemblance  to  the  original  prepara- 
tion the  new  one  was  termed  neosalvarsan. 

Physical  and  Chemical  Properties. — Neosalvarsan  is  an  orange- 
yellow  powder  of  peculiar  odor.  It  resembles  salvarsan  in  that  it 
is  very  unstable  in  the  air.  It  is  much  more  soluble  in  water  than 
the  older  preparation,  its  aqueous  solution  being  of  a  yellow  color 
of  a  depth  depending  upon  its  concentration,  and  of  neutral  reac- 
tion. Upon  standing  the  aqueous  solution  turns  a  dark  brown 
color  and  forms  a  brown  precipitate.  According  to  the  label  which 
accompanies  each  ampule  of  neosalvarsan  the  chemical  compo-. 
sition  is  dioxydiamido-arsenobenzene-monomethane-sulphinate  of 
sodium  (Ci2Hii02As2N2CH20.SONa),  together  within  organic  salts. 

The  structural  formula  may  be  represented  as  follows: 

^g :: As 


H— C  C— H  H— C  C— H 

H— C  C— NH2  H— C  C— NH(CH20)0SNa 

\    /  \    / 

c  c 

I  I 

OH  OH 

According  to  the  report  of  the  Council  on  Pharmacy  and  Chem- 
istry of  the  American  Medical  Association,^  neosalvarsan  has  the 
following  chemical  properties : 

A  precipitate  is  formed  upon  the  addition  of  mineral  acids  to 
an  aqueous  solution  (1  to  100). 

Upon  the  addition  of  a  silver  nitrate  test  solution  to  an  aqueous 
solution  of  neosalvarsan  (1  in  100)  a  brownish  color  should  be  pro- 
duced, quickly  followed  by  the  formation  of  a  black  precipitate. 
Ferric  chloride  test  solution  yields  a  violet  color  which  soon  turns 
to  a  dark  red. 

The  addition  of  5  c.c.  of  diluted  hydrochloric  acid  to  10  c.c.  of 

1  New  and  Non-official  Remedies:  Jour.  Am.  Med.  Assn.,  1912,  lix,  p.  879. 


SPECIFIC  TREATMENT  223 

an  aqueous  solution  of  neosalvarsan  (1  in  100)  and  the  application 
of  heat  produce  the  irritating  odor  of  sulphur  dioxide. 

If  5  c.c.  of  diluted  hydrochloric  acid  be  added  to  19  c.c.  of  the 
aqueous  solution  of  neosalvarsan  (1  in  100),  the  precipitate  collected 
on  a  filter  and  treated  with  zinc  dust  and  warm  diluted  hydro- 
chloric acid  in  a  test-tube,  and  if  paper  moistened  with  a  5  per 
cent,  sodium  chloride  solution  be  held  in  the  mouth  of  the  tube,  the 
paper  should  be  stained  yellow  in  a  few  minutes  (distinction  from 
salvarsan) . 

If  to  10  c.c.  of  the  aqueous  solution  of  neosalvarsan  (1  in  100) 
5  c.c.  of  diluted  hydrochloric  acid  be  added,  the  precipitate  removed 
by  filtration,  2  c.c.  of  barium  chloride  test  solution  added  to  the 
filtrate,  the  mixture  boiled  and  evaporated  to  dryness,  the  residue 
should  not  be  completely  soluble  in  50  c.c.  of  hot  water  slightly 
acidified  with  hydrochloric  acid. 

According  to  the  manufacturers,  the  arsenic  content  of  neosal- 
varsan is  less  than  that  of  salvarsan,  0.9  gram,  the  maximum  dose 
of  the  newer  preparation,  corresponding  to  0.6  gram  of  the  older 
preparation. 

Neosalvarsan  may  be  administered  subcutaneously,  intramus- 
cularly or  intravenously,  the  latter  method  being  the  most  frequently 
employed. 

Wechselmann^  is  probably  the  most  ardent  advocate  of  the  sub- 
cutaneous method  and  prepares  the  drug  for  injection  by  dissolving 
it  in  1  c.c.  of  0.9  per  cent,  salt  solution  made  from  freshly  distilled 
water. 

According  to  the  manufacturers,  neosalvarsan  should  be  used 
for  intramuscular  injection  in  approximately  5  per  tent,  dilution 
as  1  gram  of  the  drug  dissolved  in  22  c.c.  of  water  gives  an  isotonic 
solution.  Therefore  for  each  0.15  gram  3  c.c.  of  freshly  distilled 
water  should  be  used. 

Neosalvarsan  may  be  injected  intravenously  in  comparatively 
high  dilution  or  in  concentrated  solution,  the  latter  method,  how- 
ever, being  the  easier,  fully  as  free  from  untoward  effects  and 
reduces  to  a  minimum  the  danger  of  "water  faults."  The  drug 
should  be  dissolved  in  freshly  distilled  water  either  in  the  propor- 
tion of  0.15  gram  to  25  c.c.  or  0.15  to  2  c.c. 

The  water  must  not  be  hot  (not  over  20°  to  22°  C.  (68°  to  71.6° 
F.)  and  the  solution  should  be  injected  at  once. 

Salvarsan  Nairium. — A  third  preparation  has  been  produced 
by  Ehrlich  under  the  name  of  salvarsan  natrium,  or  sodiiun  salvar- 
san. This  drug,  which  has  not  yet  been  placed  upon  the  market, 
is  said  to  combine  the  intensive  action  of  the  old  salvarsan  with  the 
solubility  and  ease  of  preparation  of  neosalvarsan. 

1  Miinchen.  med.  Wchnschr.,  1913,  Ix,  p.  1309. 


H- 

C 

/   \ 

-c        c- 

1             1 

-H 

H- 

1            1 

-c        c- 

\  / 

c 

1 

OH 

-NHzNaCl 

224  TREATMENT 

It  is  produced  by  allowing  sodium  hydroxide  to  act  upon  sal- 
varsan,  thus  forming  the  di-sodium  salt,  which  is  then  precipitated 
by  proper  reagents.  The  following  represents  the  structural 
formula : 

As As 

,1  I  ". 

C 

/   \ 
H— C  C— H 

NaCl.NH2C  C— H 

\    / 
C 

OH 

Dose. — The  dose  of  salvarsan  when  first  used  was  0.3  gram, 
but  was  soon  increased  to  0.6  gram  as  the  average  amount  admin- 
istered. Neosalvarsan  is  recommended  by  the  manufacturers  in 
doses  not  to  exceed  0.9  gram,  while  an  average  of  0.6  to  0.75  gram 
for  men  and  0.45  to  0.6  gram  in  women  is  advised.  Some  workers, 
however,  have  administered  as  large  doses  as  1.2  grams  of  salvarsan 
and  1.8  grams  of  neosalvarsan.  The  tendency  nowadays  is  to  return 
to  the  smaller  doses,  and  the  author  rarely  gives  a  dose  of  over  0.4 
gram  of  salvarsan  or  0.6  gram  of  neosalvarsan.  The  rule  usually 
followed  is  to  administer  salvarsan  in  doses  of  0.006  gram  per  kilo- 
gram of  body  weight.  Thus,  a  man  of  average  weight,  about  60 
kilograms  (150  pounds),  should  receive  0.35  gram.  Clinical  experi- 
ence has  shown  that  such  doses  are  fully  as  potent  as  the  larger 
ones. 

Ehrlich's  ideal  of  therapia  magna  sterilisans  has  not  been  realized, 
as  in  the  majority  of  cases  more  than  one  dose  of  salvarsan  is 
necessary. 

Technic  of  Injection. — Salvarsan  or  neosalvarsan  for  subcuta- 
neous or  intramuscular  injection  after  preparation  should  be 
placed  in  an  all-glass  syringe  of  sufficient  capacity,  to  which  is 
attached  a  needle  of  about  20-guage.  The  usual  site  of  the  sub- 
cutaneous injection  is  the  back  between  the  scapulae,  and  the 
needle  should  be  pointed  downward. 

Intramuscular  injections  usually  are  made  in  the  gluteal  region 
at  the  upper  border  of  the  muscles.  The  nefedle  should  be  inserted 
deeply  into  the  muscle  arid  the  injection  slowly  made,  the  point 
of  the  needle  being  moved  from  time  to  time  to  ensure  a  greater 
distribution  of  the  drug. 

The  site  of  injection  for  both  the  subcutaneous  and  intramuscular 
methods  should  be  painted  with  iodin  before  injection  and  should 
be  massaged  afterward. 

A  great  many  forms  of  apparatus  for  the  intravenous  injection 


SPECIFIC  TREATMENT 


225 


of  these  drugs,  both  depending  upon  air  pressure  and  upon  gravity, 
have  been  devised  and  placed  upon  the  market. 

The  Carey  apparatus  (Fig.  50)  is  a  good  example  of  the  air-press- 
ure instruments,  but  to  the  author's  mind  the  gravity  instruments 
are  much  superior. 

The  simplest  form  of  the  gravity  type  of  apparatus  is  shown  in 
Fig.  51,  and  consists  of  a  single  graduate  cylinder,  tapering  to  the 
end  to  which  is  attached  a  piece  of  rubber  tubing  50  to  60  cm.  in 
length,  to  the  lower  end  of  which  in  turn  is  attached  a  needle  of 
suitable  gauge.  A  glass  observation  tube  may  be  placed  between 
the  needle  and  the  rubber  tubing. 

Owing  to  the  marked  toxic  effect  of  salvarsan,  and  to  a  less  extent 
of  neosalvarsan  on  the  perivascular  tissues  when  these  drugs  are 
allowed  to  escape  into  them  during  intravenous  injection,  it  is  very 
desirable  to  have  some  arrangment  to  overcome  this  danger. 


Fig.  50. — Carey  apparatus  for  intravenous  administration  of  salvarsan. 


In  the  early  days  of  salvarsan  injection  many  workers  made  it 
a  routine  procedure  to  dissect  out  a  vein  in  the  arm  before  inserting 
the  needle,  some  even  ligating  the  vein  and  inserting  a  cannula. 
This  practice,  however,  has  fallen  into  disuse,  except  in  very  rare 
instances  when  the  veins  are  so  small  or  so  obscure  that  successful 
venipuncture  otherwise  is  impossible.  In  the  past  three  years -the 
author  has  found  this  procedure  necessary  but  once. 

With  the  single  cylinder  and  rubber  tubing  the  danger  of  allow- 
ing the  drug  to  escape  into  the  perivascular  tissues  may  be  over- 
come either  by  inserting  the  needle  detached  from  the  tube  a 
successful  venipuncture  being  indicated  by  the  flow  of  blood  through 
the  needle,  attaching  the  tube  and  allowing  the  drug  to  flow,  or 
by  placing  25  to  30  c.c.  of  normal  salt  solution  in  the  cylinder, 
making  the  puncture  and  allowing  the  salt  solution  to  flow.  If 
the  solution  flows  freely  and  there  is  no  puffing  of  the  tissues  around 
15 


226 


TREATMENT 


the  needle,  the  latter  may  be  considered  as  correctly  inserted.  The 
salvarsan  then  is  poured  into  the  cylinder  and  permitted  to  flow 
into  the  vein. 

If  the  glass  observation  tube  is  used  between  the  needle  and  the 
rubber  tubing,  usually  there  will  be  a  visible  back  flow  of  blood  when 
the  needle  is  properly  inserted,  after  which  the  solution  may  be 
allowed  to  flow. 


Fig.  51. — Simple  apparatus  for  administration  of  salvarsan. 


The  salvarsan  should  be  washed  out  of  the  cylinder  and  rubber 
tubing  by  pouring  50  to  100  c.c.  of  salt  solution  into  the  cylinder 
when  but  a  few  cubic  centimeters  of  the  drug  remain  and  allowing 
it  to  run  for  a  few  seconds.  The  main  objections  to  these  methods 
are  that  when  the  needle  is  inserted  disconnected  there  is  some 
danger  of  contamination  in  making  the  connection,  also  some 
danger  of  embolism  from  clotted  blood.    When  the  glass  observa- 


SPECIFIC   TREATMENT 


227 


tion  tube  is  used  a  back  flow  of  blood  is  not  always  seen.     And 
finally,  with  either  method  an  assistant  is  necessary. 

In  order  to  overcome  all  of  these  objections  the   author   has 
devised  the  apparatus  shown  in  Figs.  52  and  53. 


Fig.  52.— Author's  apparatus  for  administration  of  salvarsan. 


This  consists  of  a  stand  {A)  adjustable  for  height,  two  glass 
burettes  {B  and  C)  of  250  c.c.  capacity.  Rubber  tubmg  connects 
the  burettes  to  a  glass  Y  ( D),  the  thb-d  arm  of  which  is  connected 
with  a  specially  devised  three-way  cock  (F)  by  means  of  50  to  bO 
cm.  of  rubber  tubing  and  a  glass  observation  tube  {E).     A  Luer 


228  TREATMENT 

needle  is  attached  directly  to  the  opposite  side  of  the  three-way 
cock,  and  the  third  opening  consists  of  an  arm  running  at  right 
angles  so  constructed  as  to  allow  the  direct  connection  of  a  glass 
observation  tube  (G).  To  the  latter  is  attached  a  small  test-tube 
(H)  by  means  of  adhesive  plaster. 

When  ready  for  use  the  salvarsan  is  placed  in  burette  B  and  nor- 
mal salt  solution  in  burette  C,  the  air  is  expelled  from  the  apparatus 
by  allowing  salt  solution  t-o  run  through  it,  and  the  lever  of  the  stop- 
cock is  turned  so  that  there  is  a  direct  connection  between  the 
needle  and  the  test-tube  ( H) .  The  stop-cock  of  burette  C  is  turned 
so  that  the  salt  solution  will  flow,  while  the  stop-cock  of  burette 
B  is  turned  so  that  the  salvarsan  will  not  flow. 

The  patient  lies  on  an  operating  table  and  extends  the  arm  on 
an  arm  rest.  The  region  of  the  elbow  is  painted  with  iodin  or  rubbed 
thoroughly  with  alcohol,  a  tourniquet  placed  around  the  arm  and 
the  patient  is  told  to  open  and  close  the  hand  a  few  times,  which 
usually  will  cause  the  veins  to  stand  out  so  prominently  that  they 
may  be  seen  or  at  least  palpated. 


Fig.  53. — Detail  of  three-way  cock  of  author's  apparatus. 

The  needle  is  then  inserted  in  the  direction  of  the  blood  stream, 
a  successful  venipuncture  being  indicated  by  the  flow  of  blood  into 
the  test-tube.  The  skin  over  the  vein  may  be  infiltrated  with  a 
little  novocain  solution,  using  a  very  fine  hypodermic  needle.  This 
reduces  the  pain  of  inserting  the  salvarsan  needle  practically  to 
nil  and  is  very  desirable,  especially  in  nervous  individuals.  The 
salvarsan  needle  should  be  very  sharp  with  a  short  bevel.  The 
tourniquet  is  then  loosened  and  the  lever  of  the  stop-cock  (F) 
so  turned  that  there  is  a  direct  connection  between  the  needle  and 
the  observation  tube  (E) .  If  the  point  of  the  needle  is  well  within 
the  lumen  of  the  vein  the  salt  solution  will  be  seen  to  flow  freely 
and  there  will  be  no  puffing  of  the  tissues  around  the  needle.  The 
salt  solution  is  then  cut  off  by  turning  the  stop-cock  of  burette 
C  and  the  salvarsan  permitted  to  flow  by  turning  the  stop-cock 
of  burette  B.  When  a  sufficient  quantity  of  salvarsan  has  run  from 
the  burette  the  stop-cocks  are  reversed  and  the  salt  solution  per- 


SPECIFIC   TREATMENT 


229 


mitted  to  run  for  a  few  seconds  to  allow  the  salvarsan  to  be  washed 
from  the  apparatus.    If  the  entire  amount  of  salvarsan  m  the  burette 
is  to  be  administered,  it  is  permitted  to  run  until  the  air  is  seen  in 
the  glass  Y,  when  the  stop-cocks  are 
reversed.    By  this  method  only  a  mini- 
mal quantity  of  salvarsan  is  wasted. 

The  salt  solution  is  not  cut  off  imtil 
the  needle  is  withdrawn,  which  is  done 
with  a  quick  jerk.  The  patient  is  in- 
structed to  raise  his  arm  for  a  few 
minutes,  a  piece  of  cotton  or  gauze  is 
applied  until  the  bleeding  ceases,  and 
the  needle  puncture  covered  with  a 
drop  of  collodion  or  a  piece  of  ad- 
hesive plaster. 

With  this  apparatus  and  using  the 
dilution  recommended,  i.  e.,  0.1  gram 
to  each  10  c.c,  it  is  possible  to  ad- 
minister fom-  doses  of  0.5  gram  in 
twenty  to  thirty  minutes  without  as- 
sistance. A  fiu-ther  advantage  of  the 
author's  apparatus  is  that  the  blood 
which  flows  into  the  test-tube  when 
the  needle  is  inserted  into  the  vein 
may  be  kept  for  the  Wassermann  test, 
which  it  is  desirable  to  have  performed 
frequently  during  the  coiU"se  of  treat- 
ment. 

For  the  injection  of  neosalvarsan  in 
concentrated  solution  the  author'^  em- 
ploys two  20  c.c.  Luer  s\Tinges  and 
the  same  stop-cock  described  above. 
Fig.  54  shows  the  method  of  connec- 
tion, and  is  almost  self-explanatory, 
salt  solution  being  used  in  one  s\Tinge 
and  neosalvarsan  in  the  other.  The 
advantage  of  using  this  stop-cock 
rather  than  those  with  rubber  con- 
nections is  that  the  entire  apparatus  is  solid  and  the  operation 
can  be  performed  in  a  minimal  time  without  assistance. 

Administraiion  by  Enferoch/sw. — A  nimiber  of  investigators 
have  administered  salvarsan  and  neosalvarsan  by  enteroclysis 
with  more   or   less  favorable  residts.     Oulmann   and  WoUheim- 


Fig.  5-1:. — ^Author's  apparatus 
for  adruinistration  of  neosalvar- 
san in  concentrated  solution. 


^  Thompson:  Jour.  Cut.  Dis.,  1915,  xxxiii.  p.  631. 
-  Jour.  Am.  Med.  Assn.,  1913,  Ixi,  p.  S67. 


230  ■  TREATMENT 

report  the  use  of  this  method  thirty-seven  times  in  thirty  cases, 
five  with  neosalvarsan  and  thirty-two  with  salvarsan.  These 
workers  dissolve  the  drug  in  exactly  240  c.c.  of  water  and  allow  it 
to  flow  into  the  bowel  through  a  rectal  tube  at  the  rate  of  one  drop 
per  second,  thus  taking  one  hour  for  the  treatment.  ■  After  their 
experience  Oulmann  and  Wollheim  reach  the  following  conclu- 
sions : 

1.  The  administration  of  salvarsan  and  neosalvarsan  by  entero- 
clysis  has  a  place  in  therapeutics. 

2.  In  general  it  ought  not  to  replace  the  intravenous  method, 
because  it  is  possible  that  in  passing  through  the  intestinal  mucous 
membrane  or  the  liver  after  absorption  some  of  the  salvarsan  may 
be  changed  chemically  and  in  that  way  its  therapeutic  effect  may 
be  less  per  unit  of  dosage. 

3.  It  should  be  used  in  children  in  preference  to  other  methods. 

4.  It  should  be  the  method  of  choice  when  the  intravenous 
method  is  not  feasible. 

5.  The  subject  is  worthy  of  further  study  to  determine  the  exact 
place  of  this  method  in  the  administration  of  salvarsan  and 
neosalvarsan. 

Advantages  of  Various  Methods  of  Injection. — Most  writers  on 
the  subject  are  agreed  that  the  subcutaneous  injection  of  salvarsan 
and  neosalvarsan  should  not  be  carried  out.  Wechselmann,i 
on  the  contrary,  is  very  insistent  that  this  is  the  method  of  choice 
in  administering  neosalvarsan,  stating  that  with  the  concentrated 
solution  he  employs  the  pain,  as  a  rule,  is  very  slight  and  that  in 
one  thousand  injections  he  has  never  seen  necrosis  result. 

The  intramuscular  injections  which  at  first  were  extensively 
employed  have  been  abandoned  very  largely  owing  to  the  intense 
pain  which  usually  follows  and  the  necrosis  which  sometimes  results. 
In  recent  years  the  oily  preparations  of  salvarsan  for  intramus- 
cular injection  have  been  exploited  quite  extensively  by  certain 
pharmaceutical  houses,  but  these  are  not  to  be  recommended,  owing 
to  the  danger  of  oxidation  as  well  as  the  pain  and  abscess  formation 
which  sometimes  occur. 

To  the  author's  mind  the  intravenous  method  is  the  one  of  choice 
in  all  cases.  The  pain  is  practically  nil,  especially  if  the  skin  is 
anesthetized  with  novocain  as  outlined  above,  and  the  technic  of 
injection  may  be  mastered  with  a  very  little  practice. 

Indications. — In  a  word,  it  may  be  said  that  salvarsan  and  neo- 
salvarsan are  indicated  in  all  cases  of  active  syphilis.  They  are, 
however,  especially  indicated  in  severe  cases  and  in  such  cases  as 
do  not  do  well  under  mercurial  treatment. 

1  Milnchen.  med.  Wchnschr.,  1913,  Ix,  p.  1309. 


SPECIFIC   TREATMENT  231 

Contraindications.^ — The  number  of  contraindications  to  the 
administration  of  salvarsan  has  gradually  narrowed.  At  first 
many  conditions  were  considered  contraindications,  such  as  marked 
debilitated  conditions,  whether  due  to  syphilis  or  not,  tuberculosis, 
nephritis,  cardiac  and  arterial  disturbances,  syphilitic  involvement 
of  the  nervous  system,  especially  optic  atrophy,  pregnancy,  high 
blood-pressure,  etc. 

Some  of  these  conditions  must  still  be  considered  as  contraindi- 
cations while  others  must  be  looked  upon  as  partial  contraindi- 
cations, that  is,  as  requiring  special  care  in  treating. 

Debilitated  conditions  should  not  be  considered  as  contraindi- 
cations to  the  use  of  salvarsan,  as  this  drug  exerts  a  tonic  effect, 
and  naturally  if  the  condition  be  due  to  syphilis  the  injection  of 
salvarsan  will  be  expected  to  cause  improvement. 

It  has  repeatedly  been  shown  that  tuberculous  individuals  with 
syphilis  often  are  benefited  materially  by  the  use  of  salvarsan.  Of 
course  in  advanced  tuberculosis  when  a  cure  is  without  the  range 
of  possibility  salvarsan  should  not  be  administered  except  for  the 
purpose  of  curing  syphilitic  symptoms. 

Nephritis  of  any  type  formerly  was  considered  a  contraindication 
to  the  administration  of  salvarsan.  If  it  can  be  shown  that  the 
nephritis  is  due  to  the  syphilis,  the  administration  of  the  drug  cer- 
tainly is  indicated.  If,  on  the  other  hand,  the  nephritis  cannot  be 
shown  to  be  due  to  the  syphilis,  salvarsan  should  be  administered 
only  with  great  caution.  Not  only  should  the  urine  be  examined 
for  albumin  and  casts,  but  the  phenolsulphonephthalein  functional 
test  should  be  applied  both  before  and  after  administering  the 
remedy,  and  the  initial  dose  should  be  very  small. 

Patients  with  marked  cardiac  lesions,  with  decompensation, 
irregular  pulse,  and  dyspnea,  if  shown  not  to  be  due  to  syphilis, 
should  not  receive  salvarsan.  If,  however,  the  condition  is  shown  to 
be  due  to  the  syphilis  or  there  is  doubt  concerning  it,  the  drug  should 
be  administered,  but  with  caution  and  in  small  dosage. 

Marked  aortic  aneurysm,  even  if  due  to  syphilis,  will  not  be 
benefited  by  the  use  of  salvarsan,  but  if  the  condition  is  not  far 
advanced  the  drug  should  not  be  withheld. 

Syphilitic  involvement  of  the  nervous  system  should  no  longer 
be  considered  a  contraindication  to  the  administration  of  salvarsan, 
although  the  possibility  of  a  Herxheimer  reaction  should  be 
considered.     (See  page  237.) 

Pregnancy  and  a  high  blood-pressure  also  are  no  longer  to  be 
considered  as  contraindications,  although  in  both  conditions  the 
dosage  should  be  small  and  administered  with  caution. 

1  The  remarks  concerning  the  contraindications  to  salvarsan  apply  as  well  to  neo- 
salvarsan. 


232  TREATMENT 

Preparation  of  Patients. — Salvarsan  or  neosalvarsan  should  not 
be  administered  on  a  full  stomach.  The  patient  therefore  should 
be  instructed  to  eat  a  light  dinner  the  evening  before  the  injection 
and  little  or  no  breakfast  the  following  morning.  The  bowels  should 
be  moved  by  a  saline  or  other  mild  cathartic.  It  need  only  be 
mentioned  that  a  thorough  physical  examination  should  be  made 
of  each  patient  and  a  urinalysis  including  a  phenolsulphone- 
phthalein  test,  performed  before  the  administration  of  salvarsan. 

After-care  of  Patient. — It  is  not  necessary  for  the  patient  to  go 
to  the  hospital  for  the  injection  of  salvarsan,  as  in  the  majority  of 
cases  it  may  be  administered  with  perfect  safety  in  the  office.  The 
patient  should,  however,  return  to  his  home  as  quickly  as  possible 
after  the  injection  and  remain  quiet  during  the  remainder  of  the 
day.  It  is  not  necessary  to  retire  unless  he  is  inclined  to  do  so. 
The  diet  should  be  light  during  the  remainder  of  the  day,  and 
individuals  who  are  inclined  to  constipation  should  receive  a  mild 
laxative. 

In  certain  cases  of  syphilis,  such  as  marked  cutaneous  lesions, 
severe  visceral  involvement,  and  syphilis  of  the  nervous  system, 
it  usually  is  advisable  to  administer  the  drug  in  the  hospital  or  in 
the  patient's  home. 

The  urine  of  the  patient  should  always  be  examined  the  morning 
following  the  injection. 

Action  of  Salvarsan. — The  injection  literally  of  millions  of  doses 
of  salvarsan  has  proved  beyond  a  doubt  the  beneficial  effect  of 
this  drug  upon  the  lesions  of  syphilis. 

Chancres,  the  syphilodermata,  and  the  syphilomycodermata 
heal  with  startling  rapidity,  the  treponemata  sometimes  disap- 
pearing from  the  lesions  within  twelve  to  twenty-four  hours,  while 
the  symptoms  of  visceral  syphilis  and  syphilis  of  the  nervous  system 
usually  diminish  and  may  disappear  altogether  following  its  use. 

The  mode  of  action  of  salvarsan  has  been  described  very  clearly 
by  Ehrlich,^  who  states  that  while  it  has  been  thought  by  some  that 
the  action  of  the  drug  is  that  of  a  stimulant  to  the  formation  of 
antibodies  which  in  turn  attack  the  treponemata,  such  is  not  the 
case,  but  that  the  salvarsan  acts  directly  upon  the  organisms 
through  the  agency  of  the  so-called  chemoreceptors. 

Salvarsan  also  undoubtedly  has  a  tonic  effect  upon  the  body, 
as  it  has  been  administered  with  favorable  results  in  anemic 
conditions  not  due  to  syphilis. 

Untoward  Effects. — Numerous  phenomena  ranging  all  the  way 
from  slight  indisposition  to  death  occur  with  more  or  less  frequency 
following  the  administration  of  salvarsan,  and  as  the  drug  may  be 

1  Lancet,  1913,  clxxxv,  p.  445. 


SPECIFIC  TREATMENT  233 

given,  and  often  is,  without  any  manifestations  whatsoever,  all 
will  be  considered  under  the  heading  of  Untoward  Effects. 

The  local  reaction  which  usually  follows  the  subcutaneous  and 
intramuscular  injection  of  salvarsan  varies  from  slight  soreness 
with  induration  to  intense  pain,  only  controlled  by  morphin, 
necrosis,  and  abscess  formation. 

It  has  been  shown  that  the  necrosis  and  abscesses,  sometimes 
at  least,  are  not  due  to  infection,  as  the  contents  are  found  sterile, 
but  to  the  direct  action  of  the  drug  on  the  tissues.  It  is,  of  course, 
possible  that  the  technic  of  injection  be  so  poor  that  microorgan- 
isms are  introduced  with  the  salvarsan  and  abscess  formation  result. 
One  such  case  came  under  the  notice  of  the  author  during  the  sum- 
mer of  1911.  The  patient,  a  prostitute,  had  been  injected  intra- 
gluteally  with  salvarsan  prepared  in  the  physician's  office  and  car- 
ried several  city  blocks  before  injection.  When  seen  by  the  author, 
three  days  later,  each  buttock  was  markedly  inflamed,  red  and 
swollen,  and  exceedingly  tender,  presenting  a  yellowish  spot  at 
the  point  of  injection.  After  painting  the  buttocks  with  iodin 
an  incision  about  1  cm.  long  was  made  in  each  and  several  ounces 
of  thick,  creamy  pus  evacuated,  which  showed  the  presence  of 
Staphylococcus  aureus. 

The  sterile  abscesses  and  necroses  which  sometimes  are  seen 
following  the  subcutaneous  and  intramuscular  injection  of  salvarsan 
may  occur  within  a  few  days  after  injection,  or  they  may  not  make 
their  appearance  until  weeks  later. 

A  patient  recently  seen  by  the  author  through  the  courtesy  of 
one  of  his  colleagues  came  to  him  two  weeks  following  the  intra- 
gluteal  injection  of  0.6  gram  of  salvarsan  into  the  left  buttock,  show- 
ing an  area  of  necrosis  6  cm.  in  diameter  but  without  suppuration. 
(Fig.  55.) 

It  often  happens,  in  fact  it  was  the  rule  with  the  majority  of  cases 
of  intramuscular  injections  made  by  the  author,  that  while  no 
abscess  formation  or  necrosis  takes  place  a  tender  induration  about 
the  size  of  a  walnut  is  formed  and  persists  in  some  cases  for  months. 

If  during  intravenous  injection  of  salvarsan  the  operator  has 
the  misfortune  to  allow  the  drug  to  escape  into  the  perivascular 
tissues  a  local  reaction,  depending  in  severity  upon  the  amount 
of  the  drug  escaping,  will  result.  If  only  a  few  drops  are  deposited 
in  the  perivascular  tissues,  usually  nothing  more  than  a  painful 
area  and  black-and-blue  discoloration  will  follow,  which  will  last 
for  a  few  days.  If,  however,  the  drug  escapes  in  considerable 
quantity,  reactions  similar  to  those  following  the  intramuscular 
injection,  with  necrosis  and  sloughing  may  be  observed.  The 
author  recently  has  had  such  a  case  under  his  care.  This  patient, 
a  woman,  aged  thirty-eight  years,  had  received  an  injection  of 


234 


TREATMENT 


salvarsan  ten  days  previous,  at  which  time,  in  order  to  find  a  vein, 
the  physician  had  made  an  incision  about  3  cm.  long  at  the  bend 
of  the  elbow. 


Fig.  5.5. — Necrosis  of  buttock  following  intramuscular  injection  of  salvarsan. 

The  vein  was  located  and  the  needle  inserted.  It,  however, 
according  to  the  patient,  became  dislodged  twice  during  the  injec- 
tion and  the  salvarsan  was  permitted  to  flow  into  the  open  wound. 
When  seen  by  the  author  a  large  sloughing,  ulcerative  area  5  cm. 
long  by  3  cm.  broad  and  8  or  10  mm.  deep,  was  observed  (Fig.  56). 
This  healed  in  about  six  weeks,  leaving  an  ugly  scar. 


Fig.  56. 


-Ulceration  following  intravenous  injection  of  salvarsan  with  escape  of 
fluid  into  perivascular  tissues. 


Certain  general  reactions  also  more  or  less  regularly  follow  the 
administration  of  salvarsan,  especially  by  the  intravenous  method. 
Probably  the  most  frequent  of  these  is  headache.  This  headache 
may,  however,  be  due  more  to  the  nervous  condition  of  the  patient 


SPECIFIC  TREATMENT  235 

than  to  the  action  of  the^  drug.  It  may  be  present  before,  during, 
or  after  the  injection,  and  is  most  frequent  in  individuals  receiving 
their  first  treatment.  There  is  no  doubt  that  headache  does  some- 
times occur  as  a  result  of  the  action  of  the  drug  itself. 

Further  in  certain  cases  of  cerebral  syphilis  in  which  headache 
is  an  almost  constant  symptom  there  may  be  an  increase  of  the 
pain  following  the  injection  of  salvarsan.  This  may  be  due  to  an 
exaggeration  of  the  syphilitic  process,  and  is  not  observed  for  twelve 
to  twenty-four  hours,  or  it  may  be  due  to  the  same  causes  which 
operate  with  the  injection  of  salvarsan  in  cases  in  which  there  is 
no  cerebral  involvement. 

Nausea  sometihies  is  observed  following  the  administration  of 
salvarsan,  and  usually  is  due  to  the  action  of  the  drug,  although 
in  certain  individuals  it  may  b^  a  purely  psychic  phenomenon. 
As  a  rule  it  passes  away  in  a  few  hours  without  ti-eatment,  and 
nearly  always  can  be  relieved  by  placing  cold  towels  on  the  throat 
and  forehead  or  by  allowing  the  patient  to  hold  a  small  piece  of  ice 
in  the  mouth.  A  little  hot  water  administered  every  ten  minutes 
sometimes  will  relieve  the  condition. 

Vomiting  also  may  occur  as  an  after-effect  of  the  administra- 
tion of  salvarsan,  although  it  is  not  so  frequent  as  it  formerly  was. 
As  a  rule  it  is  of  short  duration  and  needs  no  treatment.  It  may, 
however,  be  so  severe  as  to  require  the  use  of  morphin.  This  should 
be  administered  in  |-grain  dose  hypodermically. 

A  looseness  of  the  bowels  following  the  injection  of  salvarsan 
is  sometimes  noted.  This  has  been  ascribed  by  some  workers  to 
the  liberation  of  an  endotoxin  from  the  destruction  of  treponemata. 
With  this  theory  the  author  does  not  agree,  as  it  rarely  is  noted  if 
the  bowels  have  been  emptied  previous  to  the  injection,  and  is 
as  frequently  noted  in  mild  cases  as  in  severe  ones.  As  a  rule  this 
looseness  of  the  bowels  does  not  need  treatment,  but  if  continuous 
may  be  controlled  by  bismuth,  opium,  or  sometimes  by  an  enema. 

In  the  early  days  of  the  intravenous  injection  of  salvarsan  a 
severe  chill,  followed  by  a  distinct  rise  in  temperature,  even  to 
40.5°  or  41°  C.  (105°  to  106°  F.),  often  occurred.  This  was  shown, 
in  the  majority  of  cases,  to  be  due  to  the  use  of  old  distilled  water, 
and  since  the  adoption  of  freshly  distilled  water  for  the  preparation 
of  the  salvarsan  these  reactions  have  become  less  frequent. 

That  such  reactions  occasionally  do  occur,  however,  even  with 
the  most  careful  technic  is  attested  by  all  who  have  had  any  con- 
siderable experience  in  the  intravenous  administration  of  salvarsan. 
The  cause  of  these  reactions  is  more  or  less  a  moot  point,  some 
workers  believing  that  they  are  due  to  the  liberation  of  endotoxins 
from  the  destruction  of  the  treponemata,  while  others  affirm  that 
they  are  drug  reactions. 


236  "  TREATMENT 

Wechselmann^  states  that  it  seems  possible  that  some  of  the 
deaths  of  infants  injected  with  salvarsan  are  due  to  the  rapid 
dissolution  of  enormous  numbers  of  treponemata. 

Swift^  says  "  In  florid  syphilis  one  frequently  sees  a  fever  and  gen- 
eral malaise  following  the  first  injection  of  salvarsan.  This  picture 
is  probably  due  to  the  setting  free  of  some  toxic  substances  from 
the  spirochete."  Martin^  is  very  insistent  that  these  reactions  are 
due  to  the  liberation  of  endotoxins  from  the  killed  organisms,  and 
considers  the  rise  in  temperature,  even  of  a  fraction  of  a  degree, 
as  indicative  of  the  destruction  of  treponemata  and  that  diagnostic 
importance  can  be  placed  upon  this  reaction. 

The  author  has  seen  a  few  very  marked  reactions  follow  the 
injection  of  salvarsan  in  severe  cases  of  syphilis  when  the  technic 
of  preparation  was  perfect.  On  the  other  hand,  he  has  seen  it 
administered  in  moderately  severe  cases  of  syphilis  with  no  reac- 
tion whatsoever,  and  when  the  clinical  results  were  all  that  could 
be  desired.  He  has  therefore  reached  the  conclusion  that  the  vast 
majority  of  such  reactions  are  due  to  the  salvarsan,  although  in 
some  cases  he  is  inclined  to  believe  the  reaction  may  be  due  to  the 
liberation  of  endotoxins  from  the  treponemata.  That  diagnostic 
importance  can  be  attached  to  the  reaction  he  does  not  believe. 

Nephritis  occasionally  has  followed  the  administration  of  salvar- 
san, but  it  is  doubtful  if  a  perfectly  healthy  kidney  is  ever  very 
seriously  damaged  by  this  drug.  A  small  amount  of  albumin  and 
a  few  hyalin  casts  sometimes  are  found  in  the  urine,  especially  if 
there  has  been  a  severe  systemic  reaction,  and  such  findings  should 
indicate  the  greatest  care  in  subsequent  treatment. 

Cyanosis  and  edema  of  the  face  rarely  are  seen  following  the 
injection  of  salvarsan.  Levan*  reports  a  case  in  which  transient 
collapse  occurred  in  a  middle-aged  patient  following  the  intravenous 
administration  of  0.3  gram  of  salvarsan.  The  injection  was  followed 
at  once  by  cyanosis  and  nausea,  while  the  face  swelled  enormously 
and  the  tongue  became  so  large  it  could  not  be  protruded  between 
the  lips.  Intense  headache  and  retching  also  were  present.  All 
the  symptoms  except  swelling  of  the  face  subsided  in  twenty  min- 
utes, while  by  the  next  morning  nothing  was  left  but  edema  of  the 
eyelids.  The  pulse  and  temperature  remained  normal  through- 
out the  attack. 

Exanthemata  of  greater  or  lesser  extent  sometimes  follow  the 
administration  of  salvarsan.  The  usual  type  of  eruption  is  morbil- 
liform or  scarlatiniform,  and,  as  a  rule,  appears  from  two  to  forty- 

1  The  Treatment  of  Syphilis  with  Salvarsan,  New  York,  1911,  p.   19. 

2  Jour.  Am.  Med.  Assn.,  1912,  lix,  p.  1236. 
»  South.  Med.  Jour.,  1915,  viii,  p.  458. 

4  Med.  Klin.,  1911,  vii,  p.  849. 


SPECIFIC  TREATMENT  237 

eight  hours  following  the  injection.    It  may,  however,  be  delayed 
and  not  appear  for  a  week  or  ten  days. 

These  eruptions  in  the  vast  majority  of  cases  undoubtedly  are 
purely  drug  reactions,  although  it  is  possible  that  the  liberation  of 
endotoxins  may  in  some  cases  be  responsible  to  a  greater  or  lesser 
degree.  There  usually  is  a  rise  in  temperature  even  to  40°  or  40.5° 
C.  (104°  to  105°  F.),  while  other  symptoms,  such  as  diarrhea, 
polydipsia,  and  occasionally  nausea  and  vomiting,  may  occur. 
Marked  pruritus  and  some  edema  also  usually  are  present.  The 
treatment  of  these  eruptions  consists  of  thorough  elimination, 
the  use  of  a  light  diet,  stimulants  where  indicated,  and  the  local 
applications  of  some  such  ointment  as  zinc  stearate. 

In  one  case  seen  by  the  author  a  scarlatiniform  rash  covering 
the  entire  body  appeared  three  days  after  the  injection  of  0.6 
gram  of  salvarsan.  This  injection  was  the  fifth  this  patient  had 
received.  Following  the  fourth  injection  one  week  previous  a 
slight  eruption  resembling  miliaria,  which  condition  it  was  con- 
sidered, appeared  and  lasted  two  or  three  days.  The  rash  follow- 
ing the  fifth  injection  was  accompanied  by  intense  pruritus  and 
a  temperature  of  38.5°  C.  (101°  F.),  and  lasted  for  nearly  three 
weeks,  disappearing  with  marked  desquamation. 

The  so-called  Jarisch-Herxheimer  reaction  consists  of  an  aggra- 
vation of  the  pathological  process  in  luetic  tissues  following  the 
use  of  specific  treatment.  It  is  seen  more  frequently  following 
salvarsan  and  neosalvarsan  than  following  mercury.  The  reaction 
is  noted  in  skin  lesions,  in  lesions  of  the  mucous  membranes,  and 
in  lesions  of  the  viscera  and  nervous  tissue.  In  the  syphilodermata 
and  the  syphilomycodermata  the  reaction  manifests  itself  by  a 
redness,  more  or  less  pain,  edema  and  sometimes  fever.  Gummata 
are  swollen  and  may  ulcerate. 

Visceral  lesions  act  in  a  similar  manner.  If  the  kidneys  are 
involved,  there  will  be  an  increase  in  the  amount  of  albumin  and 
casts  present  in  the  urine. 

Liver  involvement  will  result  in  an  inflammatory  reaction  of 
the  bile  ducts  with  more  or  less  marked  symptoms  of  bile  obstruc- 
tion, such  as  yellow  conjunctivae,  clay-colored  stools,  and  bile 
pigments  in  the  urine. 

In  cases  of  syphilis  of  the  nervous  system  the  Herxheimer  reaction 
is  manifested  with  various  symptoms  depending  upon  the  location 
of  the  pathological  process.  In  cerebral  syphilis  the  reaction 
usually  is  manifested  by  an  intense  headache.  If,  however,  gum- 
mata exist,  the  reaction  may  be  manifested  by  an  exaggeration  of 
the  focal  symptoms  and  paralysis.  In  tabes  the  reaction  usually 
consists  of  intense  pains  due  to  involvement  of  the  posterior  spinal 
roots,  which  appear  from  one-half  to  one  hour  following  the  injec- 


238  TREATMENT 

tion,  and  may  last  for  twenty-four  to  forty-eight  hours.  These 
pains  may  be  so  severe  as  to  require  full  doses  of  morphin,  although 
it  has  been  noted  that  they  sometimes  are  stopped  by  the  injection 
of  another  and  smaller  dose  of  salvarsan.  When  a  cranial  nerve 
which  passes  through  a  bony  canal  is  involved  in  the  syphilitic 
process,  and  is  the  seat  of  a  Herxheimer  reaction,  the  swelling 
of  the  nerve  will  produce  symptoms  depending  upon  the  nerve 
involved.  For  example,  if  the  seventh  nerve  is  involved  as  it  passes 
through  the  aqueduct  of  Fallopius,  a  facial  paralysis  will  follow. 

Numerous  theories  have  been  advanced  to  account  for  the  Herx- 
heimer reaction,  the  best  known  of  which  are  that  it  is  due  to  the 
liberation  of  endotoxins  from  the  treponemata  and  that  it  is  due 
to  insufficient  dosage.  This  latter  theory  was  proposed  by  Ehrlich, 
who  believed  that  instead  of  the  treponemata  being  completely 
killed  they  are  stimulated  to  increased  activity  and  multiplication. 

The  provocative  Wassermann  reaction  described  in  the  chapter 
on  Laboratory  Diagnosis  should  be  considered  as  an  evidence  of 
the  Herxheimer  reaction. 

Salvarsan  Fatalities. — Soon  after  the  introduction  of  salvarsan 
it  was  learned  that  death  might  follow  its  use,  and  there  sprang 
up  a  fear  of  it  in  the  minds  of  the  laity  as  well  as  in  the  minds  of 
some  physicians  which  it  has  been  hard  to  dispel.  Probably,  how- 
ever, as  Schmitt^  pointed  out  in  1914  in  an  analysis  of  the  274 
deaths  reported  up  to  that  time,  in  a  large  proportion  of  cases 
reported  as  salvarsan  fatalities  there  is  no  connection  between  the 
drug  and  the  death. 

The  deaths  which  can  be  considered  as  due  to  the  use  of  salvarsan 
have  been  ascribed  to  various  causes.  Probably,  however,  the 
majority  have  been  due  to  faulty  technic.  The  author  has  personal 
knowledge  of  but  two  deaths  following  salvarsan,  one  of  which 
was  due  to  embolism.  The  physician,  after  inserting  the  needle 
into  one  of  the  veins  at  the  elbow  and  finding  that  the  blood  did 
not  flow  freely,  attempted  to  open  the  lumen  of  the  needle  by 
passing  a  wire  through  it.  Undoubtedly  a  blood-clot-  was  pushed 
out  of  the  needle  into  the  vein,  as  the  patient  died  before  the  dose 
could  be  administered. 

Other  errors  of  technic  which  may  result  in  death  which  may  be 
mentioned  are  inadequate  antisepsis,  air  embolism,  embolism  from 
cotton  fibers,  from  filtering  the  drug  through  cotton,  and  faulty 
preparation  of  the  drug  for  injection. 

As  pointed  out  above,  Wechselmann  considers  it  at  least  possible 
that  the  deaths  in  infants  following  the  injection  of  salvarsan  may 
be  due  to  the  liberation  of  endotoxins  from  the  killed  treponemata. 

1  Miinchen.  med.  Wchnschr.,  1914,  Ixi,  p.  1399. 


SPECIFIC  TREATMENT  239 

Other  investigators  have  thought  that  this  might  account  for  part 
of  the  deaths  in  adults. 

Wechselmann^  considers  that  some  deaths  following  the  injection 
of  salvarsan  are  due  to  the  fact  that  the  kidneys  have  been  injured 
by  previous  mercurial  treatment  and  thus  are  unable  to  eliminate 
the  salvarsan. 

Death  following  an  injection  other  than  the  first,  especially  the 
second,  has  been  ascribed  to  an  anaphylactic  phenomenon.  The 
second  death  of  which  the  author  has  personal  knowledge  occurred 
in  the  practice  of  one  of  his  colleagues  following  the  administration 
of  the  second  dose.  Albumin  and  casts  had  been  found  in  the  urine 
following  the  first  dose,  and  some  hours  after  the  injection  of  the 
fatal  dose  the  patient  fainted  when  attempting  to  go  to  the  toilet. 
There  was  complete  suppression  of  the  urine,  and  the  patient  died 
in  convulsions  on  the  third  day. 

Too  large  doses  of  the  drug  with  too  short  intervals  between 
them,  thus  resulting  in  arsenical  poisoning,  have  been  thought  to 
be  responsible  for  some  salvarsan  fatalities. 

Friiwald^  cites  29  cases  of  death  following  the  injection  of  neo- 
salvarsan,  and  asserts  that  15  undoubtedly  were  due  to  the  drug. 
In  these  cases  the  symptoms  were  those  of  a  toxic  myelitis  or 
encephalitis.  One  personal  case  belonged  to  the  latter  class.  A 
girl,  aged  eighteen  years,  healthy  except  for  an  early  syphilitic 
eruption  of  the  face,  mouth,  and  genitals,  received  an  intravenous 
injection  of  0.75  gram  of  neosalvarsan  dissolved  in  2  c.c.  of  distilled 
water.  The  dose  was  repeated  in  five  days  and  on  the  seventh  day 
the  patient  became  unconscious  and  died  in  twelve  hours. 

Brandenburg^  reports  the  case  of  a  robust  man,  aged  thirty-eight 
years  who  showed  no  symptoms  of  syphilis  four  years  after  a  thor- 
ough mercurial  treatment.  The  Wassermann  reaction  was  negative 
and  his  wife  and  children  were  healthy.  Nevertheless,  he  thought 
he  had  better  have  a  dose  of  salvarsan  as  a  prophylactic,  and  0.5 
gram  was  administered  intravenously.  Nausea,  vomiting,  and 
diarrhea  occurred  at  once  and  the  patient  died  in  convulsions  the 
fourth  day  following. 

The  Fate  of  Salvarsan  in  the  Body. — Wechselmann*  states  that 
in  the  organs  of  a  patient  dying  from  intercurrent  disease  fourteen 
days  after  the  injection  of  salvarsan  no  arsenic  could  be  demon- 
strated, although  in  the  gluteus  muscle  into  which  the  injection  had 
been  made  arsenic  was  demonstrated  in  considerable  quantity. 
In  another  case  dying  thirty-six  days  after  injection  about  0.01 

1  The  Pathogenesis  of  Salvarsan  Fatalities,  St.  Louis,  1913. 

2  Med.  Klin.,  1914,  x,  p.  1052. 

3  Ibid.,  1913,  ix,  p.  751. 

^  The  Treatment  of  Syphilis  with  Salvarsan,  New  York,  1911,  p.  86. 


240  TREATMENT 

gram  of  arsenic  was  found  in  the  gluteus  muscle.  According  to 
Wechselmann,  following  the  intramuscular  injection  of  salvarsan 
arsenic  has  been  demonstrated  in  the  blood  on  the  second  day, 
while  it  could  not  be  detected  on  the  fourteenth  day. 

During  the  intravenous  injection  of  salvarsan,  blood  withdrawn 
from  the  other  arm  can  be  shown  to  contain  arsenic. 

The  arsenic  of  salvarsan  is  excreted  through  the  urine  and  feces, 
and  its  presence  has  been  demonstrated  in  the  urine  as  early  as 
twenty-five  minutes  following  the  subcutaneous  method  of  injection, 
and  even  before  the  injection  is  completed  when  the  intravenous 
method  is  employed. 

The  length  of  time  that  arsenic  can  be  found  in  the  urine  following 
the  injection  of  salvarsan  will  depend  upon  the  method  of  injection, 
the  dosage,  and  the  condition  of  the  kidneys. 

Thus,  according  to  Wechselmann,^  the  urine  of  a  paretic  having 
received  0.3  gram  of  salvarsan  subcutaneously  showed  traces  of 
arsenic  on  the  eleventh  and  twelfth  days  following  injection,  while 
on  the  thirteenth  day  it  could  not  be  demonstrated.  On  the  other 
hand,  of  twenty-five  vigorous  syphilitics  each  receiving  0.3  gram 
subcutaneously  but  few  showed  arsenic  in  the  urine  on  the  fifth 
day,  while  by  the  tenth  day  the  urine  of  all  was  free  from  arsenic. 
Administered  intravenously  the  drug  is  eliminated  much  more 
rapidl}^  and  completely,  as  the  urine  is  found  to  be  negative  on  the 
third  or  fourth  day  following  the  injection  of  0.3  gram.  The  elimi- 
nation through  the  intestine  is  slower  than  through  the  urine. 
Following  intramuscular  injection  arsenic  may  be  demonstrated 
in  the  feces  as  late  as  the  tenth  day,  but  usually  is  no  longer  present 
after  the  fifth  or  sixth  day  following  intravenous  injection.  Kaplan^ 
states  that  some  writers  have  found  arsenic  in  the  feces  even 
after  four  weeks,  while  Finger  reports  a  case  in  which  the  drug 
could  be  demonstrated  nine  months  after  a  single  injection  of 
salvarsan. 

Comparative  Value  of  Mercury  and  Salvarsan. — A  great  deal  has 
been  written  concerning  the  relative  values  of  mercury  and  salvar- 
san in  the  treatment  of  syphilis,  and  opinions  vary  greatly.  Even 
after  five  years  of  successful  salvarsan  therapy  there  are  a  few 
physicians  who  cling  to  mercury  and  discredit  entirely  the  newer 
specific.  And,  on  the  other  hand,  after  four  hundred  years  or  more 
of  mercury  treatment  of  syphilis  there  are  some  who  claim  that  it 
is  not  a  specific  for  this  disease  and  pin  their  faith  exclusively  to 
salvarsan.      Of   these   Wechselmann^    uses    salvarsan    exclusively 

1  The  Treatment  of  Syphilis  with  Salvarsan,  New  York,  1911,  p.  84. 

2  Serology  of  Nervous  and  Mental  Diseases,  Philadelphia  and  London,  1914,  p. 
235. 

3  The  Pathogenesis  of  Salvarsan  Fatalities,  St.  Louis,  1913,  p.  143. 


SPECIFIC  TREATMENT  241 

because  he  considers  it  more  efficient  than  mercury  and  less  danger- 
ous except  when  given  following  that  drug. 

Martin^  believes  that  mercury  never  kills  the  treponemata  but 
merely  forces  them  to  retire  and  lie  dormant,  while  salvarsan  actually 
destroys  the  infecting  organisms. 

Between  this  extreme  view  and  that  of  the  exclusive  mercury 
supporters  most  syphilologists  steer  a  middle  course,  consider  both 
remedies  as  true  treponemacides  and  use  both  in  the  treatment  of 
syphilis.  Even  Ehrlich^  himself  says :  "  On  the  other  hand,  however, 
the  greater  power  of  resistance  of  certain  parasites  has  to  be  taken 
into  account,  and  this  is  a  purely  chemical  question  which  can  only 
be  solved  by  chemical  means.  The  road  leading  to  its  solution  which 
promises  the  best  results  is  that  of  combined  therapy.  .  .  . 
(Combined  therapy  is  best  carried  out  with  therapeutic  agents  which 
attack  entirely  different  chemoreceptors  in  the  parasites.)  .  .  . 
A  further  advance  of  combined  therapy  is  that  under  the  influence 
of  arsenic,  which  naturally  would  be  a  very  great  obstacle  in  con- 
nection with  further  treatment,  it  is  apparently  greatly  diminished." 

There  is  plenty  of  clinical  evidence  to  show  that  mercury  can 
cure  the  lesions  of  syphilis  and  that  these  lesions  often  never  return 
nor  do  other  manifestations  of  syphilis  appear,  the  individual 
living  to  a  ripe  old  age  apparently  free  from  syphilis.  In  the  case 
of  salvarsan  there  is  also  clinical  evidence  to  show  that  the  lesions 
of  syphilis  disappear  under  it  use,  that  in  many  cases  they  have  not 
returned  and  other  manifestations  of  syphilis  have  not  occurred; 
in  other  words,  a  clinical  cure  has  resulted.  These  facts  are  so  well 
known  that  the  quoting  of  statistics  would  be  superfluous.  It  is, 
however,  the  consensus  of  opinion  of  the  majority  of  syphilolo- 
gists that  salvarsan  is  more  potent  than  mercury  and  that  most 
of  the  lesions  of  syphilis  clear  up  more  rapidly  under  the  arsenic 
preparation  than  under  the  mercury.  The  time  since  the  intro- 
duction of  salvarsan  has  been  so  comparatively  short,  however, 
and  the  fact  that  relapses  sometimes  do  occur  makes  the  drawing  of 
definite  conclusions  from  clinical  evidence  alone  impossible.  It 
is  therefore  necessary  to  turn  to  the  laboratory  for  evidence. 

Fox^  compiled  the  records  of  twenty-one  observers,  including 
1634  cases,  most  of  which  had  been  treated  thoroughly  with  inunc- 
tions or  injections  of  mercury  and  in  all  stages  of  the  disease,  finding 
64.8  per  cent,  giving  negative  Wassermann  reactions. 

Noguchi*  reviewed  the  work  of  several  investigators  concerning 

1  Jour.  South.  Med.  Assn.,  1915,  viii,  p.  458. 

2  Lancet,  1913,  clxxxv,  p.  445. 

3  Jour.  Am.  Med.  Assn.,   1912,  lix,  p.   1243. 

^  Serum  Diagnosis  of  Syphilis,  second  edition,  Philadelphia  and  London,  1911, 
p.  136. 

16 


242  TREATMENT 

the  influence  of  mercury  upon  the  Wassermann  reaction.  He 
quotes  Citron  as  finding  81  per  cent,  of  cases  of  syphilis  positive 
before  treatment  and  65  per  cent,  positive  after  treatment.  In 
57  of  his  cases,  about  half  the  total,  but  one  course  of  treatment 
was  given. 

Bruck  and  Stern  found  81.5  per  cent,  of  173  untreated  cases  gave 
positive  reactions,  while  only  28  per  cent,  of  treated  cases  reacted 
positively. 

Blaschko  reported  45  to  52  cases  of  manifest  syphilis,  which 
before  treatment  gave  positive  reactions,  were  found  negative  after 
treatment. 

Of  211  cases  studied  by  Hoehne,  which  before  treatment  reacted 
positively  to  the  Wassermann,  56  per  cent,  became  negative  follow- 
ing mercurial  therapy.  In  5  cases  the  reaction  was  still  positive 
after  11  to  12  injections  of  mercury  salicylate  over  a  period  of  two 
months. 

According  to  Lesser  30  inunctions  of  mercury  will  cause  a  positive 
Wassermann  reaction  to  become  negative  in  about  35  per  cent, 
of  cases,  while  12  injections  of  an  insoluble  mercury  preparation 
and  25  injections  of  a  soluble  preparation  will  have  the  same  effect. 

Boas  states  that  out  of  82  cases  with  positive  reactions  76  became 
negative  following  a  course  of  injections  over  two  or  three  months. 

Matson  and  Reasoner^  found  that  in  cases  of  not  over  one  year's 
standing  the  Wassermann  reaction  became  negative  on  an  average 
in  slightly  over  two  months  under  intramuscular  injections  of 
the  red  iodide  of  mercury.  In  3  cases  treated  with  inunctions 
negative  reactions  were  obtained  in  slightly  less  time.  These 
authors,  however,  consider  that  in  a  large  series  of  cases  the  time 
for  negativating  the  Wassermann  with  inunctions  would  be  about 
the  same  as  with  the  injections.  They  also  found  that  mercury 
administered  by  mouth  required  a  longer  period  of  time  to  cause 
a  positive  Wassermann  to  become  negative. 

In  marked  contrast  to  the  above-mentioned  findings  are  the 
reports  of  Craig^  and  Nelson  and  Anderson.^  The  former  gives 
the  following  table  concering  the  Wassermann  reaction  following 
mercurial  treatment  by  mouth: 


Method  of 
treatment. 

Time  of 
treatment. 

No.  of 
cases. 

Character  of  reaction.* 

Internal 

.     9  months 

17 

+  + 
8 

+              +- 
7                 2 

Internal 

1  year 

26 

16 

8                 2 

Internal 

2  years 

17 

7 

9                 1 

Internal 

3  years 

8 

3 

4                 1 

1  Jour.  Am.  Med.  Assn.,   1911,  Ivii,  p.   1670. 

2  Bull.   No.   3,   War  Department,    Surgeon-General's   Office,    Washington,    1913, 
p.  96. 

3  Jour.  Am.  Med.  Assn.,  1915,  Ixv,  p.  1905. 

*  A  +  +  reaction  indicates  complete  inhibition  of  hemolysis. 


SPECIFIC  TREATMENT  243 

Of  18  cases  having  received  from  7  to  30  injections  of  gray  oil 
5  gave  a  +  reaction  and  the  remainder  +  +  reactions. 

The  latter  authors  report  50  cases,  all  giving  strongly  positive 
Wassermann  reactions  on  at  least  two  occasions  before  treatment, 
who  received  from  7  to  23  injections  each  of  100  mg.  (1|  grains 
of  mercury  salicylate  administered  as  often  as  possible  without  caus- 
ing salivation.  Each  patient  had  a  monthly  Wassermann  reaction 
performed,  and  while  some  showed  occasional  weakly  positive  reac- 
tions and  even  negative  ones,  all  remained  strongly  positive  at  the 
end  of  the  treatment. 

It  is  hard  to  account  for  the  marked  discrepancies  in  the  findings 
of  these  different  observers. 

The  author  has  had  comparatively  little  experience  with  the 
administration  of  mercury  alone  in  the  treatment  of  syphilis  and 
none  with  mercury  salicylate  alone,  so  he  cannot  offer  personal 
evidence  concerning  the  latter  drug.  He  has,  however,  treated 
a  few  cases  both  by  intramuscular  and  intravenous  injections  of 
soluble  preparations  of  mercury  without  other  treatment  in  which 
positive  reactions  were  changed  to  negative. 

Of  8  cases  showing  strongly  positive  Wassermann  reactions  before 
treatment  4  showed  negative  reactions  one  week  following  the  pro- 
duction of  symptoms  of  ptyalism  by  intravenous  injections  of 
mercurialized  serum.  One  case  (ulcerating  gummatous  syphilo- 
dermata)  remained  strongly  positive  in  spite  of  enough  mercur- 
ialized serum  to  produce  mild  symptoms  of  ptyalism.  The 
three  other  cases  did  not  report  for  Wassermann  tests  following 
their  mercurial  treatment. 

Of  18  cases  giving  positive  Wassermann  reactions  before  treatment 
by  intramuscular  injections  of  mercury  succinimide,  only  6  com- 
pleted their  courses  and  of  these,  4  showed  negative  Wassermann 
reactions  one  week  following  the  production  of  symptoms  of  ptyalism, 
1  a  strongly  positive  reaction  and  1  a  weakly  positive  reaction. 

Of  40  cases  with  4-plus  Wassermann  reactions  receiving  intra- 
muscular injections  of  mercury  benzoate  only  10  cases  took  treat- 
ment for  three  weeks  or  more.  Of  these  10  cases,  8  showed  nega- 
tive tests  after  from  19  to  36  injections  of  0.02  gram  of  the  benzoate. 
The  2  other  cases  received  22  and  35  injections,  respectively,  and 
the  Wasserm.ann  reaction  of  each  remained  strongly  positive. 

Of  19  cases  with  strongly  positive  Wassermann  reactions  receiving 
intravenous  injections  of  mercury  benzoate  only  5  took  treatment 
for  three  weeks  or  more.  All  of  these  5  cases  gave  negative  tests 
after  18  to  35  injections  of  0.01  to  0.02  gram  of  the  benzoate.  One 
case  was  still  strongly  positive  after  18  injections,  but  subsequently 
becam.e  negative  after  14  more  injections.  In  another  case  the 
Wassermann  was  reduced  from  a  4-plus  to  a  2-plus  by  21  injections, 
and  from  a  2-plus  to  a  negative  by  14  more  injections. 


244  TREATMENT 

All  of  these  cases  receiving  mercury  alone  were  charity  patients 
from  the  Free  Clinic  of  the  Government  Bath  House  and  were 
unable  to  pay  for  salvarsan  owing  to  the  increase  in  price  since  the 
beginning  of  the  European  War.  They  represented  nearly  all  types 
of  cases  including  chancres,  syphilodermata  and  the  so-called  latent 
cases. 

One  case  reported  through  the  courtesy  of  Dr.  William  H.  Dead- 
erick  is  worthy  of  mention.  This  patient  showed  no  manifest  symp- 
toms of  syphilis  but  gave  a  history  of  chancre  7  years  before  followed 
by  treatment  by  mouth  for  7  or  8  months  with  no  specific  treatment 
since.  His  blood  showed  a  4-plus  Wassermann  reaction  in  the 
author's  laboratory  on  August  10, 1915.  From  that  date  till  Novem- 
ber 28,  1915,  he  received  daily  injections  of  mercury  biniodide  in 
doses  of  0.005  to  0.01  gram  without  the  production  of  ptyalism  at 
which  time  his  Wassermann  reaction  was  entirely  negative  and  was 
still  negative  on  December  7,  1915,  on  December  22,  1915,  and  again 
on  April  1,  1916. 

Numerous  other  cases  which  have  been  treated  with  both  mer- 
cury and  salvarsan  have  showed  reduction  in  the  Wassermann 
following  the  mercury  but  before  the  administration  of  the  salvarsan 
and  have  later  become  entirely  negative. 

In  regard  to  the  effect  of  salvarsan  upon  the  Wassermann  reaction 
Fox^  compiled  the  results  obtained  by  thirteen  observers  in  987 
cases  treated  by  salvarsan,  finding  47.4  per  cent,  gave  negative 
Wassermann  reactions.  The  results  of  different  observers,  however, 
were  found  to  vary  from  8.8  per  cent,  to  92.3  per  cent,  of  negatives. 

Heidingsfeld^  reported  524  cases  treated  with  salvarsan  or 
neosalvarsan  or  both  in  which  74.8  per  cent,  showed  clinical  and 
laboratory  recovery.  Of  these  326  were  treated  solely  with  salvar- 
san, and  showed  74.14  per  cent,  recoveries,  and  198  were  treated 
solely  with  neosalvarsan,  with  only  67.67  per  cent,  recoveries.  It 
is  interesting  to  note  that  37  cases  which  failed  under  salvarsan 
therapy  proceeded  to  apparent  recovery  when  neosalvarsan  was 
administered  and  19  cases  in  which  neosalvarsan  had  failed  to 
cure,  recovered  under  salvarsan. 

In  this  connection  Nelson  and  Haines^  state  it  is  their  belief  that 
neosalvarsan  should  not  be  given  in  the  proportion  of  3  to  2  of 
salvarsan  as  usually  stated,  but  that  it  should  be  given  in  the 
proportion  of  6  or  8  to  2.  This  is  in  accord  with  the  author's  expe- 
rience as  he  has  found  neosalvarsan  greatly  inferior  to  the  older 
drug,  both  in  the  effect  on  the  clinical  symptoms  of  syphilis  and  in 
the  effect  on  the  Wassermann  reaction. 

1  Jour.  Am.  Med.  Assn.,  1912,  lix,  p.  1243. 

2  Urologic  and  Cutaneous  Review,  1914,  xviii,  p.  236. 

3  Jour.  Am.  Med.  Assn.,  1914,  Ixii,  p.  989. 


SPECIFIC  TREATMENT  245 

Noguchi^  reports  a  very  complete  serological  investigation  of 
102  cases  treated  with  salvarsan,  of  which  more  than  half  were  under 
observation  for  more  than  three  months  while  the  remainder  were 
injected  only  four  weeks  before  the  report  was  rnade. 

A  quantative  determination  of  the  syphilitic  antibody  content 
was  carried  out  in  each  case,  the  blood  being  examined  before  the 
injection  of  salvarsan  and  one  day,  three  days,  one  week,  two  weeks, 
four  weeks,  six  weeks,  eight  weeks,  etc.,  after  the  injection.  It  was 
found  that  30  cases  became  entirely  negative,  in  24  the  serum  was 
found  to  contain  less  than  1  antibody  unit,  while  the  remaining 
48  cases  still  contained  more  than  1  antibody  unit,  thus  giving 
strong  positive  reactions.  It  was  further  found  that  the  reduction 
of  the  Wassermann  varied  somewhat  with  the  stage  of  the  disease, 
thus  the  reaction  became  negative  in  40  per  cent,  of  the  so-called 
primary  cases,  in  37  per  cent,  of  the  secondary,  in  35  per  cent,  of 
the  tertiary,  in  33  per  cent,  of  the  latent,  in  14  per  cent,  of  the 
hereditary  and  in  50  per  cent,  of  the  incipient  tabes  cases,  with  an 
average  of  33.7  per  cent,  of  all  cases. 

In  regard  to  the  length  of  time  required  for  a  positive  Wasser- 
mann to  become  negative  following  treatment  with  salvarsan  the 
following  table  is  given  by  Noguchi: 


1  week. 

2  weeks. 

3  weeks. 

4  weeks. 

5  weeks. 

6  weeks. 

7  weeks.  Total. 

Primary  syphilis         .      0 

1 

1 

2 

1 

5 

Secondary  syphilis     .      0 

3 

5 

3 

2 

1               14 

Tertiary  syphiHs        .     0 

2 

3 

4 

2 

11 

Latent  syphihs     .      .      0 

2 

2 

Hereditary  syphilis    .      0 

1 

1 

Cerebrospinal  syphilis    0 

0 

Tabes 0 

1 

1 

0  3  10  11  5  4  1  34 

Craig^  has  made  an  exhaustive  study  of  the  effect  of  treatment 
upon  the  Wassermann  reaction  in  500  cases  and  reaches  the  follow- 
ing conclusions: 

1.  The  best  results,  as  regards  the  disappearance  of  the  reaction, 
are  obtained  in  the  treatment  of  patients  in  the  primary  stage  of 
syphilis,  and  the  poorest  in  the  treatment  of  those  in  the  tertiary 
stage. 

2.  The  reaction,  in  our  experience,  has  disappeared  most  fre- 
quently during  the  second,  third,  and  fourth  weeks  after  treatment 
with  salvarsan. 

3.  The  reaction  disappears  most  rapidly  in  patients  treated 
during  the  primary  stage. 

1  Serum  Diagnosis  of  Syphilis,  second  edition,  Philadelphia  and  London,  1911, 
p.  146. 

2  BuU.  No.  3,  War  Department,  Surgeon-General's  Office,  Washington,  1913,  p.  97. 


246  TREATMENT 

4.  The  prognosis,  as  regards  the  disappearance  of  the  reaction, 
is  most  favorable  in  those  patients  giving  a  plus-minus  reaction 
and  least  so  in  those  giving  a  double-plus  reaction. 

5.  As  regards  the  method  of  administration  of  salvarsan,  the 
best  results  have  been  obtained  for  intramuscular  injections,  and 
the  poorest  from  intravenous  injections.  However,  in  justice  to 
the  latter  method,  it  should  be  stated  that  a  vast  majority  of  the 
cases  were  given  only  one  intravenous  injection. 

6.  The  data  would  appear  to  indicate  that  at  least  three  or  four 
intravenous  injections  of  salvarsan  are  necessary  in  order  to  cause  the 
disappearance  of  the  reaction  in  from  70  to  80  per  cent,  of  patients, 
patients. 

7.  The  complement-fixation  reaction  disappears  more  rapidly 
after  the  intravenous  administration  of  salvarsan  than  after  the 
intramuscular  injection. 

8.  A  larger  proportion  of  negative  results  were  obtained  in 
patients  previously  treated  with  mercury  than  in  those  not  so 
treated,  but  the  time  of  disappearance  of  the  reaction  was  little 
affected. 

9.  The  great  superiority  of  salvarsan  over  mercury,  as  a  specific 
remedy,  was  shown  in  the  rapid  disappearance  of  the  reaction, 
after  one  or  two  injections  of  the  drug,  in  patients  previously  treated 
for  one,  two,  or  even  three  years  with  mercurials,  and  in  whom  the 
reaction  was  still  positive. 

It  will  be  seen  from  the  above  that  while  there  is  no  doubt  as  to 
the  superiority  in  some  respects  of  salvarsan  over  mercury  in  the 
treatment  of  syphilis,  the  latter  drug  certainly  has  a  place  in  the 
therapy  of  this  disease  and  should  be  used  in  practically  all  cases. 

A  word  may  be  said  here  concerning  the  effect  upon  the  Wasser- 
mann  reaction  of  the  treatment  of  syphilis  by  sodium  cacodylate. 
Heidingsf eld^  reports  that  22  cases  out  of  50,  which  before  treatment 
showed  positive  Wassermann  reactions,  became  negative  under  the 
deep  intramuscular  injections  of  this  drug  twice  weekly  for  thirty 
to  sixty  days. 

lodin.— "According  to  Lang^  iodin  was  used  in  the  treatment  of 
syphilis  soon  after  its  discovery  in  1811  or  1812.  Power^  states 
that  it  was  first  used  in  the  form  of  burnt  sponge  in  the  treatment 
of  venereal  ulcers  of  the  throat  until,  in  1821,  iodin  was  substituted 
by  Martini.  In  the  same  year  Biett  employed  iodin  with  mercury 
in  the  treatment  of  syphilodermata  and  in  1831  Lugol  published 
the  cure  of  so-called  tertiary  syphilis  treated  with  iodin  alone. 

Most  authorities  ascribe  the  first  use  of  potassium  iodide  in  the 

1  Jour.  Am.  Med.  Assn.,  1913,  Ixx,  p.  1598. 

2  Steadmann:  Twentieth  Century  Practice  of  Medicine,  New  York,  1899,  xviii, 
p.  345. 

3  System  of  Syphilis,  London,  1909,  ii,  p.  242. 


SPECIFIC   TREATMENT  247 

treatment  of  syphilis  to  William  Wallace  who  lectured  upon  its 
use  in  Dublin  in  1S3G. 

Power/  however,  states  that  this  salt  was  used  in  England  as  early 
as  1831  by  Williams.  Nevertheless  it  was  Ricord^  who  really  popu- 
larized the  use  of  potassium  iodide  and  taught  that  it  was  in  his 
tertiary  stage  of  the  disease  that  the  drug  exerted  its  greatest  influence. 

Other  preparations  of  iodin  which  have  been  employed  are  the 
similar  salts  sodium,  ammonium,  strontium  and  rubidium  iodide, 
iodoform,  iothion  and  iodol  and  the  proprietary  compounds  tiodin 
and  iodipin. 

Methods  of  Administering  Iodin. — The  most  frequently  employed 
method  of  administering  the  iodides  is  by  mouth.  The  potassium 
salt  is  the  one  most  often  used,  except  in  certain  cases  when  it  is  not 
well  tolerated  when  one  of  the  other  salts  sometimes  is  employed. 
It  has  been  claimed  that  the  rubidium  iodide  is  better  borne  by 
the  stomach. 

Potassium  iodide  may  be  administered  in  the  so-called  saturated 
solution.  That  is,  100  grams  of  the  salt  should  be  dissolved  in  a 
sufficient  quantity  of  water  to  make  100  c.c.    Thus: 

Kali  iodidi 100.0 

AquEB  destillat .      .      .     q.  s.  ad.     100.0 

It  will  be  seen  that  each  cubic  centimeter  will  contain  1  gram 
and  each  drop,  1  grain. 

The  author  usually  prescribes  it  in  10-drop  doses  t.  i.  d.,  one 
hour  after  meals  in  half  a  glass  of  water,  milk,  tea  or  other  similar 
vehicle,  the  dose  to  be  increased  each  day  by  5  drops  until  symp- 
toms of  iodism  appear.  The  patient  should  secure  a  graduate  for 
measuring  the  doses  and  as  the  dose  increases  should  be  instructed 
to  increase  the  amount  of  the  diluent.  The  reason  for  prescribing 
the  drug  one  hour  after  meals  is  that  it  is  too  irritating  to  the 
gastric  mucosa  to  be  prescribed  on  an  empty  stomach  and  if  given 
immediately  after  meals  will  act  upon  the  starch  in  the  food,  which 
in  one  hour  will  have  been  converted  into  sugar. 

Potassium  iodide  also  may  be  administered  in  pill  form  but  is 
more  poisonous  and  is  not  to  be  recommended. 

The  addition  of  ammonium  chloride  to  potassium  iodide  has 
been  said  to  increase  its  efficiency  and  the  two  drugs  sometimes 
are  prescribed  together. 

Potassium  iodide  frequently  is  prescribed  according  to  the 
formula  of  Ricord  as  follows: 

I^ — Kali  iodidi 4.0 

Syrupi  corticis  aurantii 250.0 

M.  et  Sig. — Tablespoonful  t.  i.  d. 

1  System  of  Syphilis,  London,  1909,  ii,  p.  242. 

2  A  Treatise  on  the  Venereal  Disease,  Philadelphia,  1859,  p.  503. 


248  TREATMENT 

This  disguises  the  taste  and  is  said  to  eHminate  the  griping  which 
sometimes  follows  the  use  of  potassium  iodide. 

The  iodides  also  may  be  administered  by  hypodermic  injection. 
The  usual  method  is  to  administer  the  potassium  salt  in  50  per 
cent,  solution  in  doses  of  0.25  to  0.5  gram  (4  to  8  grains).  The 
pain  which  sometimes  follows  usually  may  be  overcome  by  adding 
a  little  codein  to  the  solution. 

The  intravenous  injection  of  potassium  iodide  has  been  prac- 
tised by  several  investigators.  Doevenspeck^  administered  it  in  this 
manner,  using  a  5  per  cent,  solution  and  injecting  2  c.c.  daily. 

Wernig^  reports  the  intravenous  injection  of  sodium  iodide  in 
doses  of  10  to  30  grains  in  the  treatment  of  syphilis  with  very  satis- 
factory results. 

The  iodides  may  also  be  administered  by  enema,  and  this  method 
is  to  be  recommended  in  some  cases  when  the  stomach  does  not 
tolerate  the  drug  well.  When  administered  per  rectum  the  bowels 
should  first  be  emptied  by  a  plain  hot-water  enema  following  which 
the  iodide  should  be  injected  in  5.15-gram  doses  (Ij  to  3f  drams) 
dissolved  in  200  c.c.  (6  ounces)  of  peptonized  milk,  to  which  should 
be  added  a  few  drops  of  laudanum. 

Iodoform  sometimes  has  been  substituted  for  potassium  iodide 
and  given  either  in  pill  form  or  hypodermically.  This  drug,  however, 
has  practically  been  dropped  from  the  therapy  of  syphilis,  except 
as  a  local  application  to  specific  lesions. 

lothion  has  been  employed  as  an  inunction  quite  extensively 
by  some  workers  as  a  means  of  introducing  iodin  into  the  system, 
lothion,  the  chemical  name  of  which  is  diiodohydroryyroimn,  is  a 
yellow,  oily  fluid  containing  80  per  cent,  of  iodin.  It  is  nearly  insol- 
uble in  water  but  is  readily  soluble  in  alcohol,  ether,  chloroform, 
benzol  and  glycerin.  It  may  be  used  for  inunctions  either  pure, 
dissolved  in  alcohol  or  as  an  ointment. 

lodol  or  tetraiodipyrrol,  a  substitution  derivative  of  pyrrol,  is  a 
light  grayish-brown  powder.  It  has  been  administered  internally 
in  the  place  of  potassium  iodide  in  doses  of  0.13-0.3  gram  (2-5 
grains)  and  is  said  to  be  very  slightly  toxic. 

Tiodin  is  a  proprietary  preparation  of  iodin  and  sulphur  con- 
taining, according  to  its  manufacturers,  47  per  cent,  of  the  former. 
It  is  administered  internally  or  by  subcutaneous  injection. 

lodipin,  another  proprietary  preparation  of  iodin,  is  obtained 
by  the  action  of  iodin  chloride  on  sesame  oil.  It  is  a  yellow,  oily 
liquid  and  is  placed  upon  the  market  in  two  strengths  containing 
respectively  10  and  25  per  cent,  of  iodin.  The  10  per  cent,  solution 
is  administered  by  mouth  in  doses  of  4  to  30  c.c.  (1  dram  to  1  ounce) . 

1  Therap.  d.  Gegenw.,  1905,  xlvi,  p.  676. 

2  Jour.  Am.  Med.  Assn.,  1908,  i,  p.  609. 


SPECIFIC  TREATMENT  249 

The  25  per  cent,  solution  is  administered  either  internally  in  doses  of 
1  to  2  c.c.  (15  to  30  minims),  subcutaneously  in  doses  of  2  to  20  c.c. 
{\  to  5  drams)  or  by  rectum  in  doses  of  6  to  10  c.c.  (1^  to  2\  drams). 

lodipin  is  said  to  be  less  toxic  than  potassium  iodide  when  admin- 
istered internally  and  when  given  subcutaneously  is  not  irritating 
and  is  painless. 

While  the  majority  of  individuals  who  cannot  tolerate  a  consider- 
able amount  of  potassium  iodide  also  cannot  tolerate  greater  doses 
of  any  of  the  other  iodin  preparations,  this  is  not  always  the  case. 
It  is  therefore  well  when  symptoms  of  iodin  poisoning  are  observed 
with  comparatively  small  doses  of  potassium  iodide  to  try  with 
great  caution  one  of  the  other  preparations. 

It  has  been  suggested  that  owing  to  the  probable  different  rates 
of  absorption  of  the  various  iodin  salts  it  might  be  well  to  prescribe 
the  three,  sodium,  potassium  and  strontium  together,  thus  giving 
to  the  blood  stream  a  more  continuous  flow  of  the  iodin  ion  than 
is  obtained  with  the  administration  of  one  salt  alone. 

Therapeutic  Effects. — The  view  that  iodin  is  a  true  treponemacide 
is  held  by  but  few  syphilographers  at  the  present  time.  Nichols^ 
has  shown  that  in  experimental  syphilis  in  rabbits  the  largest  toler- 
ated dose,  0.03  gram  of  potassium  iodide  per  kilo  of  body  weight 
administered  intravenously,  has  no  effect  upon  the  treponemata. 
In  one  rabbit  with  scrotal  chancre,  however,  which  received  0.1 
gram  of  potassium  iodide  per  kilo  of  body  weight  intramuscularly 
the  treponemata  disappeared  in  eight  days  and  the  lesion  healed 
in  ten  days. 

In  experimental  work  with  monkeys  Neisser^  has  shown  that  it 
is  possible  to  prevent  syphilis  as  well  as  to  cure  it  with  doses  of  7 
to  8  grams. 

However,  in  man  there  is  abundant  clinical  evidence  to  show  that 
the  administration  of  potassium  iodide  has  little  or  no  effect  on 
chancre,  adenopathy  and  other  early  lesions  of  syphilis,  neither  does 
it  affect  the  Wassermann  reaction  by  changing  a  positive  to  a  nega- 
tive. Its  effect  on  the  luetin  reaction  has  been  discussed  in  the 
chapter  on  Laboratory  Diagnosis.  On  the  other  hand,  the  use  of 
this  drug  later  in  the  course  of  the  disease,  especially  with  gummata, 
usually  is  attended  with  favorable  results.  The  disappearance  of 
gummata  occurs  without  previous  swelling  in  contrast  to  the  action 
of  salvarsan. 

While  it  undoubtedly  is  true  that  gummata  are  "absorbed"  more 
quickly  under  treatment  with  potassium  iodide  than  without  it,  as 
Power^  states,  the  term  absorption  is  used  merely  for  convenience, 
as  the  manner  of  the  action  of  the  drug  is  unknown.    Power  quotes 

1  Jour.  Exp.  Med.,  1911,  xiv,  p.  196. 

2  Arb.  a.  d.  k.  Gsndhtsamte,  1910,  xxxvi,  p.  653. 

3  System  of  Syphilis,  London,  1909,  ii,  p.  241. 


250  TREATMENT 

French  as  believing  that  potassium  iodide  acts  "by  its  power  of 
removing  the  barricades  of  nascent  fibrous  tissue  in  which  the 
syphiUtic  virus  is  ensconced.  It  therefore  permits  the  leukocytes 
bathed  in  plasma  and  containing  an  opsonin  to  enter.  The  syphilitic 
microbe  is  thus  taken  up  or  attenuated,  and  this  explains  the  lessened 
anemia  of  the  patient." 

It  formerly  was  thought  that  potassium  iodide  administered  fol- 
lowing a  course  of  mercury  by  a  process  of  chemical  selection  united 
with  the  mercury  and  carried  it  out  of  the  body.  It  is  true  that 
potassium  iodide  stimulates  secretion  and  excretion  and  in  this 
manner  probably  assists  in  the  elimination  of  mercury. 

Some  of  the  action  of  potassium  iodide  has  been  ascribed  to  its 
stimulating  effect  on  the  thyroid,  increasing  oxidation  and  general 
metabolism  thus  increasing  the  ability  of  the  body  to  oxidize  and 
eliminate  both  the  infecting  organism  and  its  products. 

Untoward  Effects. — The  administration  of  iodin  when  pushed  to 
the  physiological  limit  is  accompanied  by  certain  symptoms  known  as 
iodism.  It  formerly  was  thought  by  many  that  syphilitics  possessed 
a  peculiar  tolerance  for  the  drug  and  that  its  administration  in  large 
dosage  without  the  production  of  iodism  was  quite  strong  evidence 
of  luetic  infection.  This  theory,  however,  has  been  disproven  as 
some  syphilitics  certainly  are  very  intolerant  to  iodin,  and  some 
non-syphilitics  are  able  to  stand  enormous  doses  without  iodism. 

Usually  the  first  symptom  of  iodism  to  appear  is  a  metafile  taste 
aptly  described  by  Keyes^  as  if  a  copper  cent  were  in  the  mouth. 
This  taste,  however,  is  noticed  by  many  even  after  a  single  dose  has 
been  administered  and  long  before  other  symptoms  of  iodism  appear. 

The  most  frequent,  and  usually  the  earliest  symptom  of  iodism 
with  the  exception  of  the  metallic  taste,  is  a  coryza,  the  so-called 
coryza  iodica.  This  may  be  mild  with  sneezing,  sensation  of  obstruc- 
tion in  the  nose  and  excessive  secretion  of  mucous  and  be  considered 
as  a  "cold  in  the  head"  or  it  may  be  severe  with  marked  swelling  of 
the  mucous  membrane  of  the  nose,  lacrimation,  pain  in  the  frontal 
sinuses,  fever  and  even  prostration. 

The  severe  types  of  coryza  usually  follow  the  administration  of 
the  first  few  doses  of  the  drug,  sometimes  even  the  first  dose,  and 
may  be  considered  as  evidence  of  an  idiosyncrasy. 

Gastro-intestinal  disturbances  often  follow  the  administration  of 
potassium  iodide  and  vary  from  slight  "indigestion"  with  heartburn 
and  loss  of  appetite  to  severe  gastro-enteritis  with  nausea,  colicky 
pains  in  the  abdomen  and  diarrhea. 

Various  dermatological  lesions  occasionally  are  observed  as  symp- 
toms of  iodism.    The  most  frequent  type  is  a  papulopustular  erup- 

1  Syphilis,  New  York  and  London,  1908,  p.  193. 


SPECIFIC  TREATMENT  251 

tion,  the  so-called  iodide  acne  which  very  much  resembles  acne 
vulgaris.  It  occurs  chiefly  upon  the  face,  forehead  and  back.  The 
lesions  consist  of  an  infiltrated  base  which  may  or  may  not  be  sur- 
mounted with  a  focus  of  pus.  Not  infrequently  several  lesions 
become  confluent.  Less  often  erythema,  eczema  and  herpes  are 
noted  and  rarely  vesicles,  bulke  and  nodules  may  be  produced. 
Sometimes  pustules  may  develop  which  pass  on  to  a  crustaceous 
stage.  Aside  from  these  inflammatory  skin  lesions  the  administra- 
tion of  the  iodides  may  produce  a  purpura. 

Other  symptoms  of  iodism  which  sometimes  are  seen  are  acute 
pains  in  the  chest,  cough,  and  dyspnea.  These  symptoms  are  due 
to  edema  of  the  upper  air  passages.  There  may  be  edema  of  the 
face  which  if  confined,  to  this  area  is  not  serious.  Edema  of  the 
upper  air  passages,  however,  has  been  known  to  cause  death. 

Iodide  salivation  may  occur,  due  to  the  action  of  the  iodin  on  the 
salivary  glands  which  may  become  markedly  swollen.  The  saliva- 
tion is  never  as  severe  as  mercurial  salivation  and  is  not  accompanied 
by  the  marked  lesions  of  the  mouth  seen  in  the  latter  condition. 

The  prevention  of  iodism  consists  of  administering  the  drug  care- 
fully and  being  alert  for  the  first  untoward  symptoms.  The  urine 
should  be  examined  daily  for  evidence  of  the  excretion  of  iodin,  in 
which  it  may  be  detected  in  a  few  minutes  after  ingestion.  A  simple 
test  for  iodin  in  the  urine  consists  of  mixing  2  c.c.  each  of  the  urine 
and  pure  hydrochloric  acid  and  adding  a  few  drops  of  chloroform. 
The  presence  of  iodin  is  indicated  by  a  pink  coloration  of  the  chloro- 
form upon  settling  to  the  bottom  of  the  tube  following  its  inversion 
two  or  three  times. 

The  failure  to  detect  iodin  in  the  urine  would  indicate  that  the 
drug  was  not  being  eliminated  and  place  the  physician  on  his  guard 
for  symptoms  of  iodism. 

It  is  often  true  that  if  mild  symptoms  of  iodism,  such  as  slight 
coryza,  appear  after  a  few  doses  of  an  iodin  preparation  that  the 
careful  continuance  of  the  drug  will  not  increase  the  symptoms,  and, 
on  the  other  hand,  they  may  disappear  not  to  reappear  until  a  very 
much  greater  amount  of  the  iodin  has  been  administered.  The 
addition  of  a  small  amount  of  belladonna  (0.01  gram  (^  grain)  to 
each  dose)  to  the  preparation  of  iodin  will  sometimes  prevent 
symptoms  of  iodism.  Arsenic  administered  with  the  iodides  also 
tends  to  prevent  iodism. 

The  treatment  of  iodism  naturally  depends  upon  its  severity. 
As  stated,  mild  symptoms  of  iodism  may  disappear  even  under  the 
continuance  of  the  drug  and  many  of  the  more  severe  symptoms 
may  require  no  other  treatment  than  the  withdrawal  of  the  iodin. 

Belladonna  or  atropine  for  the  coryza,  adrenalin  for  edema,  and  local 
treatment  of  the  dermatological  lesions  as  indicated  should  be  used. 


252  TREATMENT 

Elimination  of  lodin. — lodin  is  quickly  absorbed  and  rapidly 
eliminated.  It  has  been  found  in  all  the  secretions  and  excretions  of 
the  body,  the  urine,  the  tears,  the  milk,  the  saliva,  the  perspiration. 
It  is,  however,  mainly  excreted  by  the  kidneys.  The  time  required 
for  its  elimination  from  the  body,  as  stated  by  different  authors,  varies 
between  wide  limits.  The  following  from  the  work  of  Rountree, 
Fitz  and  Geraghty^  shows  the  amount  of  potassium  iodide  ingested 
and  the  time  required  for  complete  elimination  according  to  various 
authors : 

Author.  Amount  ingested.  Time  of  elimination. 

Geisler 0.6  gram  25  hours 

Roux 0.5"  30  hours 

Studeni 0.1      "  30  to  36  hours 

Anten 0.5       "  40  hours 

Schlayer  and  Takayasu      ...0.5"  48  hours 

Monokow 0.5       "  48  hours 

Mixed  Treatment. — The  so-called  mixed  treatment,  that  is,  the 
administration  of  mercury  and  potassium  iodide  in  the  same  solution, 
has  little  to  recommend  it.  In  the  first  place  the  use  of  mercury  by 
mouth  is  not  desirable  for  the  reasons  pointed  out  above,  and  in  the 
second  place  potassium  iodide  should  usually  be  administered  in 
increasing  doses. 

There  is  no  reason,  however,  why  the  two  drugs  should  not  be 
administered  at  the  same  time. 

SYMPTOMATIC  AND  SPECIAL  TREATMENT. 

While  there  is  more  or  less  similarity  in  the  general  and  specific 
treatment  of  all  cases  of  syphilis,  there  will  be  some  difference  depend- 
ing upon  the  portions  of  the  body  which  are  mainly  affected  and  in 
certain  cases  treatment  especially  directed  to  certain  lesions  or 
organs  is  necessary. 

Chancre. — Numerous  syphilographers  have  advocated  the 
so-called  abortion  of  syphilis  by  cauterizing  or  excising  the  chancre. 
Hunter^  probably  was  the  first  to  undertake  these  procedures 
but  did  not  consider  them  as  absolutely  certain  preventatives  of 
constitutional  syphilis,  although  he  did  think  that  in  a  large  per- 
centage of  cases  they  were  successful.  However,  in  the  light  of 
modern  knowledge  of  the  infecting  organism  such  procedures  would 
seem,  in  the  majority  of  cases  at  least,  to  be  unjustifiable.  A  chancre 
of  the  lining  mucous  membrane  of  the  prepuce  which  causes  phimosis 
usually  necessitates  circumcision  in  order  that  a  correct  diagnosis 
may  be  reached. 

That  syphilis  may  sometimes  be  aborted  when  no  other  symptoms 
but  chancre  exist  by  the  institution  of  energetic  specific  treatment  is 

1  Arch.  Int.  Med;,  1913,  xi,  p.  121. 

2  A  Treatise  on  the  Venereal  Disease,  Philadelphia,  1859,  p.  318. 


SYMPTOMATIC  AND  SPECIAL   TREATMENT  253 

undoubted.  The  first  essential,  however,  must  be  a  correct  diagnosis, 
that  is,  the  finding  of  the  Treponema  palhdum  in  the  secretion  from 
the  chancre.    Following  this  specific  medication  should  begin  atonce. 

The  local  treatment  of  chancre  is,  as  a  rule,  extremely  simple,  con- 
sisting, in  uncomplicated  genital  chancres,  of  washing  three  or  four 
times  a  day  with  warm  boric  acid  solution,  weak  bichloride  solution 
(1  to  5000)  or  potassium  permanganate  solution  (1  to  4000).  Fol- 
lowing this  the  lesion  should  be  dusted  with  aristol  or  some  similar 
dusting  powder,  and  covered  with  a  piece  of  sterile  gauze.  When 
healing  begins  or  if  crusts  form,  calomel  ointment  (10  per  cent.)  or 
hectine  (20  per  cent.)  should  be  applied. 

Chancre  of  the  urethra  may  be  cauterized  through  an  endoscope 
or  it  may  be  treated  simply  by  irrigating  the  urethra  twice  daily  with 
bichloride  solution  or  potassium  permanganate  solution.  Urethral 
suppositories  of  calomel  or  iodiform  may  be  inserted. 

Chancre  of  the  cervix  and  vagina  may  be  treated  by  douches  of 
boric  acid  and  applying  mercurial  ointment  on  tampons  or  supposi- 
tories. 

Rectal  chancres  are  best  treated  with  suppositories  of  calomel  or 
iodoform. 

Chancres  of  the  lips  and  tongue  should  be  washed  with  an  aqueous 
solution  of  bichloride  (1  to  6000)  or  painted  with  an  ethereal  solution 
of  the  same  (1  to  20). 

Tonsillar  chancres  may  also  be  painted  with  the  ethereal  solution 
of  bichloride  or  a  gargle  or  spray  of  the  aqueous  solution. 

Other  extragenital  chancres  should  be  treated  in  a  similar  manner 
to  genital  chancres. 

Chancre  complicated  by  chancroid,  the  so-called  mixed  sore, 
should  be  treated  as  if  the  syphilitic  infection  did  not  exist,  that  is, 
some  form  of  cautery  should  be  employed.  The  author  has  found 
the  following  procedure  very  satisfactory:  The  parts  are  first  thor- 
oughly cleansed  with  warm  water  and  dried,  after  which  the  lesions 
are  "ringed"  with  vaseline.  Cocaine  crystals  are  next  applied  to  the 
sore  and  removed  with  sterile  water  after  remaining  in  contact  two 
or  three  minutes.  Pure  carbolic  acid  is  next  applied  with  a  cotton 
pledget  on  an  applicator  and  after  remaining  a  minute  or  two  pure 
nitric  acid  is  applied  by  means  of  a  glass  rod  and  allowed  to  remain 
in  contact  two  or  three  minutes  when  the  excess  is  removed  with 
a  pledget  of  cotton  and  a  dry  dressing  of  aristol  applied. 

Phagedenic  chancre  should  be  treated  by  cautery  with  chromic 
acid,  or  the  actual  cautery.  In  the  majority  of  cases  general  anes- 
thesia is  necessary,  as  the  cauterization  must  be  thorough  to  be 
effective.  Following  the  cautery  the  lesion  should  be  dressed  with 
an  antiseptic  solution  and  when  the  slough  which  forms  is  removed 
dusting  powders  such  as  aristol  or  iodoform  may  be  applied. 


254  TREATMENT 

Lymphatic  Glands. — The  adenitis  following  chancre  as  a  rule 
requires  no  local  treatment.  If  complicated  by  pyogenic  infection, 
the  painting  of  the  skin  over  the  gland  with  tincture  of  iodin  may 
suffice,  but  if  suppuration  exists  it  may  be  necessary  to  incise  the 
gland,  currette  and  apply  a  dressing  of  aristol. 

The  adenitis  occurring  later  in  the  course  of  the  disease  needs  no 
local  treatment. 

Cutaneous  Lesions. — No  local  treatment  of  the  m.acular  syphilo- 
dermata  is  necessary.  The  same  may  be  said  of  the  majority  of  the 
papular  eruptions.  The  palmar  and  plantar  syphilodermata,  how- 
ever, should  receive  applications  of  an  ointment  such  as  the  official 
unguentum  hydrargyri  nitratis.  The  author  has  found  bichloride  col- 
lodion painted  on  these  lesions  very  satisfactory.  The  following 
formula  from  Lang^  may  be  used : 

I^ — Hydrarg.  chlor.  corros 0.05-0.2  (gr.  f-iij) 

Collodii 

Aeth.  sulph aa  10.0  (Siiss) 

01.  olivse 0.2  (miij) 

Moist  papular  lesions  and  condylomata  should  be  washed  once  or 
twice  daily  with  bichloride  solution  (1  to  4000)  or  carbolic  acid 
solution  (1  per  cent.),  dusted  with  aristol,  calomel  or  salicylic  acid, 
and  covered  with  sterile  gauze.  The  application  of  strong  nitric 
acid  followed  by  a  dusting  powder  sometimes  is  beneficial. 

Pustular  syphilodermata  are  best  treated  with  daily  mercurial 
vaporizations  or  mercurial  baths.  The  method  of  administering 
mercury  vapors  has  been  described  above.  The  mercurial  baths 
should  be  prepared  by  adding  2  to  16  grams  (^  to  4  drams)  of  the 
bichloride  to  30  gallons  of  warm  water  and  the  patient  should  remain 
in  the  bath  ten  to  fifteen  minutes.  Some  absorption  of  the  mercury 
is  likely  to  occur,  so  the  patient  should  be  watched  carefully  for 
symptoms  of  ptyalism,  especially  if  he  is  receiving  mercury  by  some 
other  method.  The  crusts  of  pustular  syphilodermata  may  be 
softened  with  warm  boric  acid  solution  and  removed.  An  ointment 
such  as  ammoniated  mercury,  oleate  of  mercury  (5  to  10  per  cent.) 
unguentum  hydrargyrum,  or  resorcin  (5  to  10  per  cent.)  should  be 
applied  on  gauze  twice  daily. 

Nodular  syphilodermata  which  have  not  ulcerated  as  a  rule  need 
no  local  treatment.  When,  however,  ulceration  has  taken  place  the 
methods  outlined  for  the  pustular  lesions  are  applicable. 

Gummata  of  the  skin  seen  before  ulceration  also  need  no  local 
treatment.  It  has  been  suggested  that  painting  these  lesions  with 
iodin  or  the  injecting  of  some  mercurial  or  iodin  preparation  directly 
into  the  gumma  or  around  it  will  aid  in  their  resolution.     These 

1  Steadman:  Twentieth  Century  Practice  of  Medicine,  New  York,  1899,  xviii, 
p.  361. 


THE  CURE  OF  SYPHILIS  255 

procedures,  however,  have  not  been  successful  in  the  hands  of  the 
author. 

Ulcerating  gummata  of  the  skin  may  sometimes  be  treated  suc- 
cessfully by  the  methods  outlined  above  for  the  treatment  of  the 
pustular  syphilodermata.  These  lesions,  however,  not  infrequently 
are  most  refractory.  In  such  cases  cauterization  with  silver  nitrate 
or  even  the  actual  cautery  or  the  use  of  a  curette  may  start  the 
healing  process.  Chronic  leg  ulcers  may  be  stimulated  to  healing 
by  "nicking"  the  entire  edge  of  the  ulcer  at  intervals  of  2  to  4  mm. 
with  a  pair  of  sharp  scissors  and  by  means  of  adhesive  plaster 
strapping  the  edges  back. 

Syphilis  of  the  Appendages  of  the  Skin. — In  syphilitic  alopecia 
local  treatment  is,  as  a  rule,  of  little  or  no  avail ;  the  condition  gen- 
erally improving  under  the  specifics.  The  scalp,  however,  should, 
be  shampooed  once  or  twice  weekly  following  which  a  little  vaseline 
should  be  well  rubbed  in. 

In  onychia  and  paronychia  the  lesions  should  be  kept  scrupu- 
lously clean  and  washed  twice  daily  with  bichloride  solution  (1  to 
2000) .  Following  this  a  mild  mercurial  ointment  or  dusting  powder 
should  be  applied.    Loose  nails  should  be  removed. 

Mucous  Membranes. — The  lesions  of  the  mucous  membranes 
as  a  rule  require  little  or  no  local  treatment  beyond  that  of  strict 
cleanliness.  When  occurring  in  the  mouth  the  use  of  mouth  washes 
and  gargles  such  as  potassium  chlorate  and  tincture  of  myrrh  several 
times  daily  is  to  be  recommended.  Rough  places  on  the  teeth  should 
be  removed,  and,  as  stated  above,  the  use  of  tobacco  should  be 
curtailed  as  much  as  possible.  Very  hot  foods  or  those  highly 
seasoned  should  be  avoided,  as  in  some  cases  they  irritate  and  aggra- 
vate the  condition.  Severe  lesions  may  be  touched  with  a  silver 
nitrate  stick  or  a  5  to  10  per  cent,  solution  every  three  or  four  days. 

THE  CURE  OF  SYPHILIS. 

As  a  general  rule,  to  which  there  are  exceptions,  it  may  be 
stated  that  the  older  the  syphilis,  the  more  difficult  will  be  its  cure, 
and  as  it  is  upon  the  specific  treatment  that  we  must  rely  for  the 
cure  of  this  disease,  ordinarily  more  of  such  treatment  must  be 
administered  in  late  cases  than  in  early  ones. 

The  author  urges  all  syphilitics,  no  matter  at  what  time  in  the 
course  of  the  disease  they  are  seen  to  submit  to  a  spinal  puncture, 
so  that  if  evidence  of  central  nervous  system  involvement  is  found 
specific  treatment  may  be  directed  toward  it. 

In  the  author's  practice  as  soon  as  chancre  is  diagnosed  salvarsan 
is  administered  intravenously  in  dosage  according  to  the  patient's 
weight,  that  is,  0.006  gram  per  kilo.    The  following  day  either  intra- 


256  TREATMENT 

muscular  or  intravenous  injections  of  mercury  (usually  the  benzoate) 
are  begun.  These  are  continued  until  slight  symptoms  of  ptyalism 
appear,  or  until  the  urine  shows  evidence  of  kidney  irritation,  the 
urine  being  examined  daily.  Salvarsan  is  administered  weekly  for 
four  doses,  the  mercury  being  omitted  on  salvarsan  days.  Blood  is 
collected  for  the  Wassermann  reaction  at  the  time  of  the  adminis- 
tration of  each  dose  of  salvarsan  and  if  found  positive  at  the  fourth 
injection  a  fifth  is  given,  and  so  on  until  it  is  found  negative.  If 
negative  at  the  fourth  injection,  a  fifth  is  not  given.  Local  and 
general  treatment  are  carried  out  as  outlined  above. 

Following  the  administration  of  the  last  dose  of  salvarsan  one 
month  is  allowed  to  elapse  without  treatment,  other  than  hygienic, 
when  a  Wassermann  test  is  made.  If  this  one  is  negative,  three  more 
tests  are  made  six  months,  twelve  months  and  eighteen  months 
respectively  later.  If  all  of  these  are  negative  and  no  further  symp- 
toms of  syphilis  have  appeared  at  any  time,  the  patient  is  considered 
as  probably  cured.  However,  in  order  to  pass  an  absolutely  positive 
opinion  concerning  the  cure,  the  spinal  fluid  must  be  found  normal 
on  at  least  two  occasions  one  year  apart.  If  any  of  the  Wassermann 
tests  are  found  positive  or  any  other  symptoms  of  syphilis  develop, 
the  treatment  is  repeated. 

Berstein^  has  suggested  that  all  cases  of  syphilis,  whether  showing 
involvement  of  the  central  nervous  system  or  not,  should  receive  an 
intraspinal  injection  of  salvarsanized  serum  as  a  prophylactic  meas- 
ure to  such  involvement.  The  author  considers  such  a  procedure 
as  entirely  rational. 

The  later  manifestations  of  syphilis  are  treated  specifically  in  a 
similar  manner  to  the  chancre,  although  as  might  be  expected,  two  or 
more  "courses"  of  mercury,  often  many,  with  four  to  six  weeks' 
interval,  and  several  more  injections  of  salvarsan  must  be  adminis- 
tered to  effect  a  "cure."  Potassium  iodide  also  is  used  when  gum- 
mata  or  arteritis  are  present.  Local,  symptomatic  and  special  treat- 
ments are  administered  when  indicated  and  will  be  discussed  in  Part 
II  under  the  proper  headings.  The  same  standard  for  cure  is  required 
for  all  cases  as  is  required  when  the  chancre  alone  is  present  except 
those  showing  involvement  of  the  central  nervous  system.  (See 
page  355.) 

It  is  a  well-known  fact,  however,  that  in  certain  cases  of  syphilis 
the  Wassermann  reaction  remains  positive  in  spite  of  the  most 
thorough  and  long-continued  treatment,  although  all  clinical  evi- 
dence of  the  disease  has  vanished.  To  the  author's  mind  such  cases 
cannot  be  considered  as  cured;  they  should  frequently  visit  the 
physician  for  physical  examination  and  should  take  periodic  courses 
of  treatment. 

1  Jour.  Am.  Med.  Assn.,  1914,  Ixii,  p.  914. 


PART  II. 

CHAPTER  XI. 
SYPHILIS  OF  THE  CIRCULATORY  SYSTEM. 

HEART. 

Pathology. — Syphilis  of  the  heart  has  long  been  recognized.  All 
three  layers,  pericardium,  endocardium  and  myocardium  have  been 
observed  as  the  seat  of  the  disease. 

Pericardium. — Syj^hilitic  ijericarditis  is  of  comparatively  frequent 
occurrence  and  usually  follows  myocardial  involvement.  Gummata 
of  the  pericardium  also  are  rarely  primary  but  usually  extend  from 
the  muscular  tissue  of  the  heart. 

Endocardium. — Syphilitic  endocarditis  resembles  toxic  endocar- 
ditis more  than  it  does  the  infective  form.  The  Treponema  pallidum 
infiltrate  the  connective  tissue  of  the  endothelium,  rather  than  grow 
on  the  surface  as  do  bacteria.  Here  the  organisms  produce  a  chronic 
inflammation  which  results  in  more  or  less  deformity.  The  aortic 
valve  is  most  frequently  affected,  and  when  the  mitral  is  involved 
the  process  is  usually  an  extension  from  the  aortic.  Occasionally  the 
entire  endocardium  may  be  involved.  Gummata  of  the  endocardium 
are  sometimes  observed  and  usually  extend  to  the  myocardium. 

Myocardium. — Warthin^  has  made  a  very  exhaustive  study  of 
syphilitic  myocarditis,  both  of  the  congenital  and  the  acquired  types 
of  the  disease  and  considers  both  farencliymatous  and  interstitial 
involvement.  LTnder  the  'parenchymatous  variety  he  describes:  (1) 
the  finding  of  large  colonies  of  treponemata  either  in  the  tissue 
spaces  or  about  the  bloodvessels  but  showing  no  recognizable  tissue 
change;  (2)  pale  degeneration  of  the  heart  muscle  which,  he  says, 
is  probably^ to  be  interpreted  as  being  of  the  nature  of  a  serous 
atrophy  or  liquefaction  necrosis;  (3)  fatty  degeneration,  which  is 
often  the  only  lesion  associated  with  colonies  of  treponemata.  It 
is  a  focal  change  seen  macroscopically  as  yellowish  pinhead  spots, 
but  aj-e  often  larger.  Microscopically  there  is  atrophy  of  the  fibers 
which  are  filled  with  large  fat  droplets.    This  focal  fatty  degenera- 

1  Am.  Jour.  Med.  Sc,  1914,  cxlvii,  p.  667. 
17 


258  SYPHILIS  OF   THE  CIRCULATORY  SYSTEM 

tion  may  be  followed  by  calcification;  (4)  simple  atrophy  of  the 
muscle  fibers  may  be  associated  with  the  treponemata.  Under  the 
interstitial  changes  Warthin  noted:  (1)  Edema  which  consists  of 
either  pale,  translucent  and  moist  areas  or  of  such  a  condition  of  the 
entire  heart  wall.  Microscopically  the  muscle  fibers  are  pushed 
apart,  the  reticulum  fibrillated  and  containing  fine  granules  and  an 
increase  of  the  number  of  wandering  cells  is  noted.  The  apparently 
edematous  areas  are  filled  with  treponemata  and  the  presence  of  a 
mucus-like  substance  is  more  suggestive  of  myxedema.  (2)  Inter- 
stitial proliferation  which  may  he  the  first  recognizable  lesion.  It  is 
always  primarily  vascular  or  perivascular.  New  vessels  are  pro- 
duced but  are  quickly  obliterated  by  the  proliferation  of  the  endo- 
thelium. Treponemata  are  found  in  large  numbers  in  the  perivas- 
cular lymphatics.  Later  these  areas  may  become  fibroid  and  may  be 
interpreted  as  non-caseating  gumma  when  sharply  localized. 

Clinical  History. — Syphilitic  pericarditis  is  rarely  recognized  clin- 
ically, although  it  not  infrequently  is  observed  at  autopsy.  The 
condition  may  be  either  acute  or  chronic  and  may  occur  at  nearly 
any  time  during  the  course  of  the  disease.  The  principle  symptoms 
are  precordial  pain  and  distress,  irregular  and  feeble  cardiac  action 
and  dyspnea.  A  friction  sound  may  or  may  not  be  present.  As  far 
as  the  author  is  aware  pericarditis  with  effusion  has  not  been 
observed. 

Endocarditis  may  occur  early  in  the  course  of  syphilis  but  gum- 
mata  of  the  endocardium  may  develop  late. 

The  symptoms  of  endocarditis  will  depend  upon  the  location  and 
extent  of  the  syphilitic  process.  As  stated  above,  the  aortic  valve  is 
most  frequently  affected  and  a  stenosis  is  the  usual  result.  In  such 
cases  there  is  generally  a  systolic  murmur  transmitted  to  the  vessels 
of  the  neck.  Aortic  incompetence  may,  however,  be  observed. 
When  the  mitral  valve  alone  is  the  seat  of  the  pathology,  which  is 
rare,  there  is  usually  a  murmur  presystolic  in  time  and  not  trans- 
mitted. 

Myocarditis  is  one  of  the  most  important  of  all  syphilitic  affections 
and  undoubtedly  is  of  frequent  occurrence.  It  may  be  present  early 
in  the  course  of  syphilis,  and  as  pointed  out  above,  treponemata  may 
even  be  found'  in  the  heart  wall  without  any  demonstrable  tissue 
change.  It  is  therefore  easy  to  imagine  syphilitic  involvement  of 
the  heart  without  any  clinical  symptoms  of  the  disease.  However, 
when  the  process  is  extensive  enough  to  cause  tissue  change  the 
symptoms  will  be  many  and  varied. 

Undoubtedly  the  most  frequent  symptom  is  dyspnea  and  it  is 
most  varied  in  degree,  sometimes  not  being  present  except  on  unac- 
customed physical  exertion  and  again  may  be  so  severe  as  to  cause 
the  patient  marked  distress. 


HEART  259 

Other  symptoms  are  precordial  pain  and  tenderness,  irregular 
cardiac  action,  cyanosis,  decompensation  and  even  heart-block. 
Following  the  latter  condition  the  bundle  of  His  has  been  found 
affected  with  gummata. 

Paroxysmal  pain  of  an  anginal  character  accompanied  by  a  symp- 
tom of  terror,  ashy  countenance  and  marked  prostration  has  been 
described. 

Diagnosis. — Most  frequently  the  patient  with  heart  syphilis  pre- 
sents himself  to  the  physician  with  the  complaint  of  symptoms 
referable  to  the  heart  but  with  no  thought  of  syphilis.  More  rarely 
the  involvement  of  the  heart  is  discovered  by  the  physician  upon 
examining  the  patient  who  presents  himself  for  treatment  of  syphilis 
of  other  portions  of  the  body.  The  diagnosis  of  cardiac  syphilis  is 
seen  from  this  to  depend  upon  two  factors,  the  diagnosis  of  heart 
disease  and  the  recognition  of  the  syphilitic  etiology  of  the  con- 
dition. 

Thus  it  is  encumbent  upon  the  internist  to  think  of  syphilis  in  all 
cases  of  disease  of  the  heart  and  to  recognize  its  presence  or  to 
exclude  it  from  the  etiology.  Likewise  the  syphilologist  must 
examine  the  heart  most  carefully  and  recognize  its  involvement  in 
all  cases  of  syphilis. 

The  symptomatology  of  syphilis  of  the  heart  does  not  differ  from 
the  symptomatology  of  cardiac  disease  due  to  other  causes.  The 
diagnosis  will  therefore  depend  upon  the  history,  which  when  nega- 
tive is  of  little  value,  the  presence  or  absence  of  other  manifestations 
of  syphilis,  the  laboratory  evidence  and  therapeutic  tests.  It  must 
be  understood  that  the  presence  of  cardiac  disease  in  an  individual 
undoubtedly  syphilitic,  both  clinically  and  from  a  laboratory  stand- 
point, does  not  prove  the  heart  condition  to  be  due  to  syphilis.  The 
improvement  of  the  cardiac  symptoms  under  antisyphilitic  treat- 
ment will,  however,  be  very  strong  presumptive  evidence  that  such 
is  the  case. 

Prognosis. — It  must  be  said  that  the  prognosis,  of  syphilitic  heart 
disease  as  with  most  syphilitic  visceropathies,  depends  upon  the 
date  at  which  it  is  recognized  and  the  extent  of  the  process.  How- 
ever, the  fact  remains  that  even  extensive  heart  involvement  with 
marked  symptoms,  including  murmurs,  sometimes  yield  in  a  remark- 
able manner  to  proper  treatment.  Probably  the  prognosis  of  syph- 
ilitic heart  disease  is  more  favorable  in  the  vast  majority  of  cases 
than  is  heart  disease  of  other  etiology.  Nevertheless  in  all  instances 
a  guarded  statement  as  to  the  outcome  should  be  made  and  a  too 
sanquine  picture  should  not  be  painted  until  the  result  of  specific 
therapy  is  noted. 

Treatment. — The  treatment  of  syphilitic  heart  involvement  con- 
sists of  treating  the  heart  and  treating  the  syphilis.    The  latter  of 


260  SYPHILIS  OF   THE  CIRCULATORY  SYSTEM 

course  consists  of  specific  medication,  and  in  the  involvement  of  the 
heart  early  in  the  course  of  the  disease  usually  is  all  that  is  necessary. 
Later  when  symptoms  of  cardiac  involvement  are  marked  treat- 
ment directed  toward  the  condition  of  the  heart  is  indicated.  Most 
cases  are  best  treated  with  rest  in  bed  and  such  heart  stimulants  as 
strophanthus,  digitalis,  camphor,  strychnine  and  adrenalin  should  be 
administered  as  indicated.  Salvarsan  should  be  administered  in 
small  doses  when  decompensation  exists. 
f 

ARTERIES  AND  VEINS. 

Pathology. — Aorta. — The  aorta  when  attacked  by  the  Treponema 
pallidum  presents  certain  changes  which  even  grossly  are  fairly 
characteristic.  While  the  ascending  aorta  and  the  arch  are  most 
frequently  involved  any  portion  may  be  the  seat  of  the  syphilitic 
pathology.  Usually  the  process  is  quite  circumscribed  but  may  be 
diffuse. 

Syphilitic  Aortitis. — Usually  small  pale  gray,  elevated  patches 
varying  in  size  from  5  mm.  to  2  or  3  cm.  in  diameter  are  seen.  On 
section  they  are  observed  to  be  of  a  grayish  color,  while  beneath 
are  opaque  yellow  streaks.  Sometimes  later  in  the  disease  the 
patches  are  much  larger  and  may  encircle  the  entire  vessel.  The 
surface  is  very  irregular.  The  wall  of  the  vessel  is  usually  thinned 
and  small  bulgings  are  often  seen.  If  the  process  is  very  extensive, 
diffuse  dilatation  or  saccular  aneurysm  is  observed.  In  very  old 
cases  atheroma  may  be  present. 

Microscopically  in  the  early  cases  the  adventitia  shows  infiltration 
of  round  cells  around  the  vasa  vasorum.  Minute  new  formed  blood- 
vessels, surrounded  by  infiltrated  small  round  cells,  plasma  cells  and 
epithelioid  cells  are  seen  in  the  media.  The  endothelial  cells  of  the 
intima  are  more  or  less  proliferated.  In  the  more  advanced  cases  the 
infiltration  around  the  vessels  of  the  adventitia  is  very  marked,  while 
in  the  media  are  seen  areas  of  coagulation  necroses  which  are  sur- 
rounded by  small  round  cells  and  plasma  cells  and  are  in  reality 
gummata.  Giant  cells  are  also  usually  seen.  The  endothelial  cells 
of  the  intima  are  markedly  proliferated.  The  elastic  tissue  is  more 
or  less  destroyed,  as  seen  by  the  use  of  Weigert's  stain.  Treponemata 
are  found  more  or  less  plentifully  scattered  through  the  thickened 
intima.  Darling  and  Clark^  have  shown  that  the  syphilitic  process 
in  the  aorta  may  be  so  extensive  as  to  occlude  this  vessel  completely 
and  to  obliterate  the  lumen  of  some  of  its  larger  branches. 

Smaller  Arteries. — The  Treponema  pallidum  may  attack  either 
the  adventitia  or  the  intima  of  the  smaller  arteries  or  both  may  be 
affected  at  the  same  time.    Thus  the  media  may  be  involved  from 

1  Jour.  Med.  Research,  1915,  xxvii,  p.  1. 


ARTERIES  AND   VEINS  261 

either  or  both  sides.  The  process,  as  with  that  in  the  aorta,  consists 
of  a  low  grade  of  infiltration  of  the  endothelial  cells  of  the  intima  and 
there  is  narrowing  or  even  complete  occlusion  of  the  lumen. 

Veins. — The  adventitia  of  the  veins  is  more  frequently  invaded 
by  the  Treponema  pallidum  than  the  intima,  and  periphlebitis  fol- 
lows. When  the  intima  is  attacked  a  thrombophlebitis  usually 
results.  The  process  tends  to  progress  along  the  course  of  the  veins 
or  to  advance  from  one  vein  to  another.  The  lumen  of  the  vessel 
usually  remains  open,  except  in  the  smaller  veins.  Occasionally  the 
veins  may  be  the  seat  of  gummata  and  in  the  case  of  superficial  ones 
may  appear  as  small  reddened  nodes  along  the  course  of  the  vein. 

Clinical  History. — Aorta. — ^The  symptoms  of  syphilis  of  the  aorta 
will  depend  upon  the  severity  of  the  pathological  process.  The 
involvement  of  the  aorta  by  syphilis  is  usually  described  as  occurring 
late  in  the  course  of  the  disease,  but  there  is  no  doubt  but  that  the 
treponemata  early  invade  the  blood  stream  and  it  is  reasonable  to 
infer  that  they  early  attack  the  aorta.  In  fact  Brooks^  has  reported 
a  case  of  perforation  of  an  aneurysm  of  the  aorta  before  the  skin 
eruption  had  fully  appeared  and  another  case  with  sufficient  patho- 
logical change  in  the  aorta  to  cause  death  within  six  months  after 
infection.  This  early  evidence  of  syphilitic  involvement  of  the 
aorta  is  nevertheless  rare  and  the  length  of  time  elapsing  from  the 
date  of  infection  to  the  onset  of  symptoms  is  stated  as  varying  from 
three  to  fifty-four  years. 

The  principal  symptoms  of  syphilitic  aortitis  are  pain,  either  pre- 
cordial or  anginal,  dyspnea,  palpitation  and  tachycardia.  The 
patient  may  be  the  subject  of  violent  attacks  of  dyspnea  which  last 
from  ten  to  fifteen  minutes.  The  dyspnea  is  expiratory  and  is  accom- 
panied by  sibilant  and  crackling  rales.  There  is  also  usually  sweat- 
ing and  cyanosis,  while  the  blood-pressure  may  be  markedly  raised. 
When  aneurysm  follows  syphilitic  aortitis  the  symptoms  will  depend 
upon  the  location  of  the  lesion. 

Fever  of  a  mild  degree  is  often  an  accompaniment  of  this  condi- 
tion. Certain  physical  signs  such  as  pulsation  on  palpation,  areas 
of  dulness  on  percussion,  and  murmurs  on  auscultation  will  be 
found  depending  upon  the  location  and  severity  of  the  condition. 

Smaller  Arteries  and  Veins. — ^The  symptoms  accompanying 
syphilis  of  the  smaller  arteries  and  veins  will  depend  upon  the  ones 
affected  and  the  extent  of  the  process.  If  obliteration  occurs  in  an 
artery  supplying  a  comparatively  small  region  and  the  conditions 
are  favorable  for  the  development  of  collateral  circulation,  there  may 
be  no  symptoms.  If,  however,  a  terminal  artery  be  affected  or  many 
arteries  be  involved,  there  will  be  diminished  nutrition  and  necrosis. 

1  Med.  Rec,   1912,  Ixxxi,  p.  351. 


262  SYPHILIS  OF   THE  CIRCULATORY  SYSTEMi 

Syphilitic  phlebitis,  if  of  the  superficial  veins,  may  cause  swelling, 
pain  and  tenderness,  and  in  certain  cases  edema. 

Diagnosis. — The  diagnosis  of  syphilitic  aortitis  is,  as  a  rule,  com- 
paratively easy,  although  certain  cases  may  present  the  greatest 
difficulty.  Dyspnea,  which  is  expiratory  in  character,  with  pain, 
either  precordial  or  anginal,  and  aortic  aneurysm,  especially  of  the 
•ascending  portion  or  arch  as  revealed  by  the  .r-rays,  occurring  in  an 
individual  of  middle  life  or  younger,  will  be  suspicious,  even  in  the 
absence  of  positive  history  or  other  manifestations  of  syphilis.  How- 
ever, the  final  diagnosis  must  rest  upon  laboratory  procedures  and 
therapeutic  tests. 

Syphilitic  arteritis  and  phlebitis  cannot  be  diagnosed  upon  clinical 
evidence  alone,  but  the  indirect  evidence  of  history,  other  manifes- 
tations of  syphilis,  positive  laboratory  findings  and  therapeutic  tests 
will  clear  up  the  diagnosis  in  the  majority  of  cases. 

Prognosis. — Aorta. — The  prognosis  of  syphilitic  aortitis  is  always 
bad,  although  this  too  will  depend  upon  the  time  of  its  recognition 
and  the  extent  of  the  process. 

In  Longcope's^  series  of  63  cases  of  syphilitic  aortitis  death 
occurred  in  38,  and  in  34  of  them  was  due  directly  to  the  syphilis, 
giving  a  mortality  of  54  per  cent.  Of  the  34  cases  of  death  8  died 
suddenly  in  an  attack  of  angina  pectoris  or  paroxysmal  dyspnea  and 
the  remainder  of  cardiac  failure. 

Smaller  Arteries  and  Veins.  The  outcome  of  syphilitic  involve- 
ment of  smaller  arteries  and  veins  will  depend  upon  the  above-men- 
tioned features  as  well  as  upon  the  location  of  the  vessels  involved. 

Treatment. — Aorta. — Syphilitic  aortitis  should,  as  a  rule,  be  treated 
in  bed  and  aside  from  the  specific  treatment  should  receive  stimu- 
lants as  indicated.  As  with  heart  syphilis,  salvarsan  should  be 
administered  with  caution  and  in  small  doses  if  decompensation 
exists. 

Smaller  Arteries  and  Veins. — Syphilis  of  the  smaller  arteries  and 
veins  as  a  rule  need  no  treatment  other  than  specific  and  general. 

1  Arch.  Int.  Med.,  1913,  ii,  p.  15. 


CHAPTER  XII. 
SYPHILIS  OF  THE  RESPIRATORY  TRACT. 

LARYNX. 

Pathology. — The  syphilitic  lesions  which  attack  the  mucous 
membrane  of  the  larynx  have  been  described  in  Part  I  in  the  chap- 
ter on  Clinical  History.  Gummata  of  the  deeper  structures  of  the 
larynx  are  of  comparatively  frequent  occurrence.  Thus,  the  peri- 
chondrium of  the  laryngeal  cartilages  may  be  involved  followed 
by  necrosis. 

Clinical  History. — The  involvement  of  the  larynx  by  the  syphilo- 
mycodermata  will  produce  symptoms  depending  upon  the  extent 
of  the  process.  There  is  usually  more  or  less  hoarseness  which 
may  increase  to  aphonia  and  there  may  or  may  not  be  coughing, 

Gummata  of  the  deeper  structures  of  the  larynx  may  cause  edema 
and  marked  dyspnea  and  may  ulcerate,  causing  great  deformity 
upon  healing  due  to  cicatricial  contraction. 

Diagnosis. — The  diagnosis  of  the  syphilitic  lesions  of  the  larynx 
occurring  early  in  the  course  of  the  disease  is  usually  attended  with 
little  or  no  difficulty,  owing  to  the  usual  coexistence  of  syphiloder- 
mata  or  lesions  of  the  mucous  membranes  of  the  mouth,  throat, 
etc.  If  these  are  not  present  and  the  history  of  chancre  is  not 
obtained,  a  diagnosis  of  syphilis  may  not  be  made,  although  the 
Wassermann  test  at  this  time  is  usually  positive. 

Gummata  seen  before  ulceration  are  scarcely  to  be  mistaken  for 
any  other  condition.  Ulcerating  gummata  of  the  larynx  may,  how- 
ever, be  mistaken  for  tuberculosis  or  carcinoma.  In  tuberculosis 
there  is  more  cough,  expectoration  and  greater  difficulty  of  swallow- 
ing than  in  syphilis.  The  ulceration  of  tuberculosis  is  also  more 
superficial  and  diffuse  than  syphilitic  ulceration  and  is  accompanied 
by  more  pain.  The  progress  of  tuberculous  ulceration  is  not  so 
rapid,  as  a  rule,  as  syphilis.  Further,  the  demonstration  of  tubercle 
bacilli,  either  by  stained  smears  or  by  animal  inoculation  can 
usually  be  accomplished  in  tubercular  laryngitis.  It  must,  however, 
be  remembered  that  syphilis  and  tuberculosis  of  this  region  not 
infrequently  coexist. 

Carcinoma  of  the  larynx  should  be  differentiated  from  gumma 
by  the  fact  that  in  carcinoma  there  is  more  hemorrhage  than  in 
gumma,  the  progress  of  carcinoma  is  more  rapid  and  the  breath 


264  SYPHILIS  OF   THE  RESPIRATORY  TRACT 

is  more  foul.  The  final  diagnosis  of  syphilitic  laryngitis  will, 
however,  depend  upon  the  positive  laboratory  evidence  and  the 
improvement  of  the  condition  under  specific  therapy. 

Prognosis. — The  prognosis  of  the  healing  of  syphilomycodermata 
of  the  larynx  is  the  same  as  that  of  the  syphilomycodermata  else- 
where. There  may,  however,  be  permanent  injury  to  the  voice, 
depending  upon  the  severity  and  extent  of  the  process  following 
the  healing  of  these  lesions.  Not  infrequently  singers  find  that 
their  ability  to  sing  has  been  greatly  impaired  or  entirely  lost 
following  syphilis  of  the  larynx. 

The  prognosis  of  gummata  of  the  deeper  structures  of  the  larynx 
is  most  grave.  The  danger  of  edema  of  the  glottis  must  be  thought 
of  and  deformity  and  more  or  less  stenosis  will  follow  the  healing 
of  ulcerating  gummata. 

Treatment. — The  local  treatment  of  laryngitis  due  to  the  syphilo- 
mycodermata consists  of  insufflations  of  calomel  or  iodol,  steam 
inhalations,  mild  alkaline  sprays  and  applications  of  weak  solutions 
of  silver  nitrate  or  argyrol.  Rest  of  the  voice  is  also  desirable. 
When  ulcerating  gummata  exist  local  cleansing  with  irrigations  and 
swabs  and  the  application  of  stronger  solutions  of  silver  nitrate 
are  indicated. 

The  local  edematous  membrane  which  sometimes  is  present  should 
be  punctured,  while  abscesses  should  be  incised.  In  severe  cases  of 
edema  and  dyspnea  tracheotomy  may  be  necessary.  The  cica- 
tricial deformities  and  obstructions  sometimes  following  the  healing 
of  syphilis  of  the  larynx  may  be  relieved  by  incisions  and  resections 
performed  with  the  aid  of  the  laryngoscope,  followed  by  the  use  of 
dilators.  Of  course  specific  medication  and  general  treatment 
must  be  employed, 

TRACHEA   AND  BRONCHI 

Pathology. — Syphilitic  lesions  of  the  trachea  and  bronchi  are 
rather  rare  and  are  usual 'y  extensions  from  the  larynx  or  lungs. 
Papular  lesions  alone  or  in  association  with  similar  conditions  in 
the  mouth  are  occasionally  observed.  Gummata,,  either  diffuse 
or  circumscribed,  and  encroaching  upon  the  lumen  of  the  tubes 
have  also  been  described. 

Clinical  History. — In  syphilis  of  the  trachea  and  bronchi  the  symp- 
toms will  depend  upon  the  extent  and  severity  of  the  condition. 
If  very  extensive  and  ulceration  is  present,  a  tickling  sensation  will 
be  felt  in  the  throat  which  gives  rise  to  a  cough.  A  mucopurulent 
secretion  accompanied  by  rales  and  occasionally  pain  behind  the 
sternum  will  be  observed.  There  may  be  narrowing  of  the  trachea 
with  dyspnea. 


THE  LUNGS  265 

Gummaia  may  ulcerate  and  perforate  into  the  esophagus  or  one 
of  the  large  bloodvessels. 

Diagnosis. — The  diagnosis  of  syphilis  of  the  trachea  and  bronchi 
will  depend  upon  the  recognition  of  lesions  of  these  regions  by 
physical  examination,  tracheoscopy  and  bronchoscopy,  and  the 
differentiation  of  tuberculosis;  the  latter,  as  a  rule,  may  be  accom- 
plished by  the  usual  laboratory  tests,  and  the  administration 
of  specific  remedies. 

Prognosis. — The  prognosis  of  syphilis  of  the  trachea  and  bronchi 
depends  upon  the  location  and  extent  of  the  lesions.  If  diagnosed 
before  ulceration  has  taken  place,  healing  may  occur  with  little  or 
no  stenosis.  If,  however,  ulceration  has  taken  place,  more  or  less 
stenosis  is  bound  to  follow  and  the  prognosis  becomes  correspond- 
ingly grave.  The  situation  is  rendered  more  serious  if  the  lesion 
is  low  down  in  the  trachea  or  in  the  bronchi,  when  death  may  occur 
from  asphyxiation  or  from  complications  in  the  lungs. 

According  to  Conner^  in  Vierling's  list  of  46  cases  of  syphilis  of 
the  trachea  and  bronchi  deaths  occurred  in  39,  while  of  Conner's 
own  series  of  80  cases  there  were  58  deaths,  thus  giving  a  mortality 
for  the  128  cases,  or  76  per  cent.  The  causes  of  death  in  the  58 
fatal  cases  of  Conner's  series  were  as  follows:  19  from  some  form 
of  pneumonia,  2  of  these  being  due  to  the  inhalation  of  food  particles 
after  perforation  of  the  esophagus;  11  from  a  paroxysmal  suffo- 
cative attack;  4  from  sudden  profuse  hemorrhage  from  perforation 
of  one  of  the  large  bloodvessels.  In  most  of  the  remaining  cases 
death  was  due  to  gradual  exhaustion  and  gradual  cardiac  failure, 
while  in  a  few  cases  it  was  due  to  syphilis  of  other  parts  of  the  body 
or  intercurrent  disease. 

Treatment. — ^Vigorous  antisyphilitic  therapy  is  indicated  in 
syphilis  of  the  trachea  and  bronchi.  In  administering  the  iodides 
the  tendency  of  the  latter  drugs  to  cause  edema  of  the  mucous 
membrane  of  these  regions  must  be  remembered.  Inhalations  of 
mercurial  vapors  may  also  be  used. 

Stricture  of  the  trachea  and  bronchi  sometimes  may  necessitate 
the  use  of  dilators  while  dyspnea  due  to  stricture  of  the  trachea 
in  its  upper  portion  may  be  relieved  by  tracheotomy.  Following 
the  tracheotomy  the  stricture  may  be  dilated  by  passing  instru- 
ments through  the  wound. 

THE  LUNGS. 

Pathology. — Syphilis  of  the  lung  is  considered  rare  by  most 
syphilographers,  but  undoubtedly  numerous  cases  of  this  condition 

1  Am.  Jour.  Med.  Sc,  1903,  cxxvi,  p.  57. 


266  SYPHILIS  OF   THE  RESPIRATORY   TRACT 

have  been  diagnosed  pulmonary  tuberculosis.  Osier  and  Gibson' 
state  that  of  twenty-five  hundred  autopsies  at  Johns  Hopkins 
Hospital  only  twelve  showed  lesions  of  the  lungs  believed  to  be 
syphilitic. 

Two  types  of  syphilis  of  the  lung  are  usually  described,  diffuse 
interstitial  fibrosis  and  gummata. 

The  former  condition  consists  of  more  or  less  marked  cellular 
infiltration,  usually  starting  in  the  interstitial  connective  tissue  and 
the  walls  of  the  arteries  and  bronchi.  There  is  also  hyperplasia 
of  connective  tissue  and  swelling  and  desquamation  of  the  epithelium 
of  the  alveoli.  The  process  is  found  more  especially  in  the  hilus  of 
the  lung.  It  may  be  general  and  cause  fibrosis  and  shrinkage  of 
large  portions  of  the  lungs  or  it  may  be  confined  to  comparatively 
small  areas.  It  is  usually  unilateral  but  may  be  found  in  both 
lungs. 

Gummata  of  the  lung  occur  as  nodules  varying  in  size  from  one 
or  two  millimeters  to  several  centimeters  and  are  usually  quite 
numerous.  When  seen  in  their  earlier  stages  they  are  grayish  red 
or  grayish  white  and  surrounded  by  an  area  of  congestion.  Later 
they  may  become  soft,  necrosed  and  opaque  and  are  usually  walled 
off  by  connective  tissue,  or  they  may  rupture  into  a  bronchus. 
Instead  of  necrosis  a  fibrosis  may  trke  place.  Microscopically 
there  is  nothing  in  the  gummata  of  the  lungs  to  distinguish  them 
from  gummata  of  other  regions. 

As  far  as  the  author  is  aware  treponemata  have  not  been  demon- 
strated in  the  pulmonary  lesions  of  acquired  syphilis,  but  there  is 
every  reason  to  believe  that  they  are  present.  However,  according 
to  Osier  and  Gibson,^  Buchanan  found  them  in  the  sputum  of 
a  patient  with  undoubted  pulmonary  syphilis. 

Osier  and  Gibson^  describe  a  syphilitic  phthisis  consisting  of 
formation  of  fibrous  tissue,  gummata,  and  pneumonic  affections 
leading  to  cavitation  and  bronchiectasis. 

Clinical  History. — Although  syphilis  of  the  lung  is  comparatively 
rarely  found  at  autopsy,  it  is  of  more  frequent  occurrence  than  the 
autopsy  records  would  seem  to  indicate.  The  difficulty  in  distin- 
guishing between  syphilis  and  tuberculosis  postmortem  may  in  a 
measure  account  for  this.  The  condition  may  develop  at  nearly 
any  time  during  the  course  of  the  disease  but  is  usually  a  late 
manifestation,  being,  as  a  rule,  observed  from  three  to  ten  years 
following  the  infection. 

The  symptomatology  of  syphilis  of  the  lung,  will  vary  with  the 
extent  and  nature  of  the  process. 

>  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  iii,  p.  15. 
2  Ibid.,  p.  24.  3  Ibid.,  p.  19. 


PLEURA  267 

Diffuse  interstitial  fibrosis  of  the  lung  will  sometimes  cause  symp- 
toms markedly  resembling  pulmonary  tuberculosis. 

The  most  frequent  symptom  is  cough,  which  may  be  mild  or 
severe.  The  sputum  is  usually  mucopurulent  in  character  and  may 
be  scanty  or  profuse.  It  may  contain  elastic  tissue  and  may  be 
tinged  with  blood.  Marked  hemoptysis  sometimes  occurs.  There 
may  be  chills  in  the  afternoon  followed  by  more  or  less  fever,  the 
temperature  sometimes  reaching  41°  C.  (106°  F.)  or  over,  as  in 
a  case  reported  by  Roussel.^  The  temperature  may  also  become 
subnormal. 

Night-sweats  are  not  found  in  pulmonary  syphilis,  as  a  rule,  but 
do  sometimes  occur  and  may  be  of  a  drenching  character.  There 
is  usually  more  or  less  l6ss  of  weight,  sometimes  extreme  cachexia, 
but  the  patient  may  be  well  nourished.  Depending  upon  the  area 
involved  there  will  be  dulness,  increased  vocal  fremitis,  broncho- 
vesicular  breathing  and  rales. 

Gummaia  of  the  lung  may  or  may  not  give  rise  to  physical  signs 
and  symptoms,  depending  upon  their  size  and  location.  The  most 
frequently  noted  symptom  is  a  cough,  usually  of  trivial  character. 
The  physical  signs  of  consolidation,  dulness,  increased  vocal  fre- 
mitus, rales,  etc.,  may  be  present  if  the  gummata  are  large  or 
numerous. 

Diagnosis. — Syphilis  of  the  lungs  must  be  differentiated  from 
pulmonary  tuberculosis.  In  syphilis  night-sweats  are  infrequent  and 
cachexia  is  not  so  marked  as  in  tuberculosis.  The  final  diagnosis, 
however,  must  be  made  upon  the  absence  of  tubercle  bacilli  from 
the  sputum,  perhaps  the  finding  of  the  Treponema  pallidum,  positive 
Wassermann  or  luetin  test  and  the  improvement  of  the  condition 
under  specific  therapy 

Prognosis. — Syphilis  of  the  lungs  is  always  of  grave  import,  but 
the  prognosis  will  depend  upon  the  extent  of  the  involvement. 
Marked  improvement  and  cure  sometimes  follow  even  extensive 
pulmonary  syphilis. 

Treatment. — Aside  from  specific  and  general  treatment  the  inhala- 
tion of  mercurial  vapors  is  indicated  in  pulmonary  syphilis.  Other 
treatment  is  symptomatic. 

PLEURA. 

Syphilitic  involvement  of  the  lung  usually  leads  to  thickening 
of  the  pleurae.  Gummata  of  the  pleurae  have  been  described  by 
Lancereaux.^ 

1  New  York  Med.  Jour.,  1913,  xcviii,  p.  600. 

2  Traite  de  la  Syphilis,  1873,  p.  326. 


CHAPTER  XIII. 
SYPHILIS  OF  THE  G ASTRO-INTESTINAL  TRACT. 

THE   MOUTH    AND    PHARYNX. 

Pathology. — The  pathology  of  the  lesions  of  the*  mucous  mem- 
brane of  the  mouth,  pharynx  and  lips  has  been  described  in  Part 
I,  but  aside  from  those  conditions  the  muscles  of  the  tongue  and  lips 
may  be  the  seat  of  syphilitic  infiltration,  causing  more  or  less  swell- 
ing and  deformity.  Gummata  of  the  tongue,  hard  and  soft  palates 
and  walls  of  the  pharynx  are  sometimes  observed. 

Clinical  History. — The  symptoms  accompanying  syphilis  of  the 
mouth  and  pharynx  will  depend  upon  the  extent  of  the  process. 
There  may  be  more  or  less  burning,  difficulty  in  eating  and  talking, 
or  it  may  even  be  impossible  to  carry  out  these  functions. 

Gummata  of  the  hard  palate  often  break  down,  causing  perfora- 
tion into  the  nasal  cavity,  while  gummata  of  the  soft  palate  and 
uvula  not  infrequently  cause  destruction  of  these  tissues. 

Gummata  of  the  posterior  wall  of  the  pharynx  may  ulcerate  and 
cause  grave  complications,  such  as  involvement  of  the  cervical 
vertebrae,  hemorrhage  from  eroded  vessels,  and  such  marked 
deformities  as  to  cause  eating  to  be  most  difficult. 

These  manifestations  as  a  rule  occur  late  in  the  course  of  the 
disease,  but  Long^  reports  a  case  of  perforation  of  the  velum  two 
months  after  the  chancre. 

Diagnosis. — The  diagnosis  of  the  syphilomycodermata  of  the 
mouth  and  pharynx  has  been  sufficiently  discussed  under  the  diag- 
nosis of  these  lesions  in  Part  I. 

The  diagnosis  of  gummata  of  these  regions  as  a  rule  presents 
little  difficulty,  but  should  rest  upon  the  history,  and  laboratory 
findings.  If,  however,  these  are  negative  and  a  diagnosis  of  cancer, 
tuberculosis  or  actinomycosis  cannot  be  made  specific  therapy  should 
be  given  a  trial,  when  improvement  would  indicate  that  the  condition 
is  syphilitic 

Prognosis. — The  prognosis  of  the  syphilomycodermata  of  the 
mouth  and  pharynx  has  been  discussed  in  Part  I.  The  prognosis 
ef  gummata  of  these  regions  depends  upon  the  stage  of  the  process. 
If  seen  early  before  marked  ulceration  has  occurred,  the  prognosis 

1  Twentieth  Century  Medicine,  New  York,  1899,  xviii,  p.  104. 


THE  ESOPHAGUS  269 

should  be  good,  and  even  if  the  process  has  become  quite  extensive 
it  may  be  arrested,  although  cicatrization  may  result  and  cause 
marked  deformity. 

Treatment. — The  treatment  of  syphilis  of  the  mouth  and  phar^'nx, 
aside  from  the  specific  and  general  treatment  consists  of  the  use  of 
mouth  washes  and  gargles  and  the  surgical  removal  of  sloughing 
tissue. 

THE   ESOPHAGUS. 

Pathology. — Syphilis  of  the  esophagus  has  been  considered  a 
rather  rare  condition,  but  Wile^  after  reviewing  the  literature  and 
reporting  an  additional  case  seen  in  his  practice  considers  it  prob- 
ably not  so  rare  as  might  be  assumed  from  the  meager  literature 
on  the  subject.  According  to  this  writer,  superficial  erosions  and 
ulcers  such  as  found  in  the  mouth  and  pharynx  during  the  early 
course  of  the  disease  have  not  been  described  in  the  esophagus. 
However,  he  thinks  that  they  may  occur.  The  process  described 
is  a  gummatous  one,  located  in  the  submucosa.  Here,  either  under 
treatment  or  spontaneously,  involution  by  fatty  degeneration  may 
occur.  ,  Usually  without  treatment  and  sometimes  in  spite  of  the 
same,  early  ulceration  takes  place.  Healing  of  the  ulcers  leaves 
a  scar  and  marked  tendency  to  contraction  and  resulting  stenosis; 
or  instead  of  localized  scarring  and  contraction  there  may  be  a 
diffuse  process  which  involves  the  entire  circumference  of  the 
esophagus  for  a  greater  part  of  its  length  with  resulting  contraction, 
almost  completely  closing  the  liunen  and  preventing  the  passage 
of  solid  food. 

Clinical  History. — Syphilis  of  the  esophagus  will  yield  symptoms 
dependent  upon  the  extent  of  the  process.  There  is  more  or  less 
difficulty  in  swallowing,  at  first  probably  noticed  only  on  swal- 
lowing solids,  but  later  liquids  will  also  cause  difficulty.  Pain 
may  or  may  not  be  present,  but  is  usually  noticed  only  on  swallow- 
ing. There  is  generally  more  or  less  anemia  and  cachexia  due,  in 
part  perhaps,  to  the  general  syphilitic  infection,  but  probably  more 
to  the  inability  to  swallow  sufficient  food. 

Diagnosis. — Syphilis  of  the  esophagus  may  present  considerable 
difficulty  of  diagnosis  and  must  be  differentiated  from  carcinoma, 
spastic  stenosis  and  pressure  on  the  esophagus  by  tumors  of  the 
mediastinum. 

Carcinoma,  as  a  rule,  occurs  later  in  life  than  s;yT)hilis,  is  of  more 
rapid  development,  causes  more  cachexia,  usually  is  more  painful, 
more  frequently  provokes  emesis  and  hematemesis  and  is  more 
common  in  the  lower  portion  of  the  esophagus  than  the  upper. 

1  Am.  Jour.  Med.  Sc,  1914,  cxl\'iii,  p.  180. 


270         SYPHILIS  OF   THE  GASTRO-INTESTINAL   TRACT 

The  location  and  extent  of  the  lesion  is  determined  by  the  a;-rays, 
while  the  Wassermann  and  luetin  tests  are  valuable  in  establishing 
the  presence  or  absence  of  syphilis. 

Prognosis. — The  prognosis  of  syphilis  of  the  esophagus  will  depend 
upon  the  extent  of  the  process.  If  it  is  recognized  before  ulceration 
has  taken  place,  the  latter  may  not  occur  if  specific  medication 
is  administered.  However,  if  ulcers  have  formed,  and  they  may 
form  even  in  spite  of  the  most  vigorous  treatment,  their  healing 
will  result  in  scarring  with  contraction  and  more  or  less  stenosis. 

Treatment. — Following  the  healing  of  syphilitic  lesions  of  the 
esophagus,  which  in  favorable  cases  will  occur  under  specific 
therapy,  the  esophagus  should  be  sounded  carefully  and  if  contrac- 
tion exists,  should  gradually  be  dilated  with  esophageal  bougies. 

THE    STOMACH   AND   INTESTINES. 

Pathology. — Until  comparatively  recent  years  syphilis  of  the 
stomach  was  considered  a  rare  condition.  However,  it  is  now  recog- 
nized as  a  not  uncommon  occurrence  and  numerous  papers  on  the 
subject  have  appeared.  According  to  Osier  and  Gibson^  acute 
syphilitic  gastritis  has  been  described,  but  they  state  that  little  is 
known  concerning  the  anatomy  of  the  condition.  These  authors 
further  state  that  Virchow  first  described  chronic  syphilitic  gastritis. 
Other  pathological  changes,  as  seen  in  syphilis  of  the  stomach,  are 
gummata  and  diffuse  infiltration  of  the  stomach  wall.  Gummata 
usually  start  in  the  submucosa,  the  process  later  involving  the  other 
coats.  The  gummata  may  break  down  and  form  ulcers,  and  the 
ulcers  upon  healing  produce  cicatrices  and  perhaps  stenosis.  The 
ulcer  may  perforate  the  stomach  wall,  causing  peritonitis.  Diffuse 
syphilitic  infiltration  of  the  stomach  wall  has  been  noted  rarely 
and  causes  more  or  less  thickening. 

Microscopically  syphilis  of  the  stomach  shows  cellular  infiltra- 
tion, especially  around  the  bloodvessels,  which  are  more  or  less 
thickened  by  hyperplasia  of  the  endothelial  cells.  Treponemata 
were  not  found  in  the  cases  reported  by  Curtis^  and  McNeiP  and 
as  far  as  the  author  is  aware  have  not  been  demonstrated  in  gastric 
syphilis. 

Syphilis  of  the  intestine  presents  pathological  appearances  similar 
to  those  observed  in  the  stomach.  Duodenal  syphilis  may  extend 
from  the  stomach. 

Rectal  syphilis  is  more  frequently  observed  than  is  syphilis  of 
other  portions  of  the  gastro-intestinal  canal.  The  rectum  may  be 
the  seat  of  the  chancre.    Condylomata  and  papules  are  also  found 

1  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  iii,  p.  37. 

2  Jour.  Am.  Med.  Assn.,  1909,  Hi,  p.  1159.  ^  Ibid.,  1914,  Ixiv,  p.  430. 


THE  STOMACH  AND  INTESTINES  271 

here.  Gummata,  however,  are  the  most  frequent  syphiHtic  lesions 
of  the  rectum.  The  process  begins  in  the  submucosa  and  usually 
leads  to  marked  ulceration.  In  severe  cases  the  mucosa  may  be 
destroyed  for  a  distance  of  10  to  12  centimeters  above  the  anus. 
Later  the  ulceration  leads  to  cicatrization  with  stricture  of  the 
rectum.  Perirectal  gummata  may  disintegrate  and  form  fistulse 
into  the  rectum,  vagina  or  perineum. 

Clinical  History. — Syphilitic  gastritis  is  found  early  in  the  course 
of  the  disease,  usually  during  the  first  year,  and  presents  no  symp- 
toms differing  from  those  found  in  other  forms  of  chronic  gastritis. 
There  is  more  or  less  pain,  belching,  achylia,  loss  of  weight,  etc. 

Gummata  of  the  stomach  will  cause  symptoms  depending  upon 
their  size,  location  and  condition.  If  a  gumma  of  considerable  size  be 
present,  it  may  be  palpated.  Dyspeptic  symptoms  are  also  usually 
present.  The  tumors  may  be  situated  at  the  pyloris  and  may  cause 
stenosis  with  the  resulting  symptoms  of  dilatation,  stagnation,  etc. 

Ulcerating  gumma  which  is  the  most  frequent  syphilitic  lesion 
of  the  stomach  usually  causes  symptoms  very  closely  resembling 
ulcer  of  the  stomach  due  to  other  causes  than  syphilis.  There  is 
usually  more  or  less  pain  after  eating,  and  there  may  or  may  not  be 
vomiting.  Hemorrhage  is  frequent,  while  diminished  or  absent 
hydrochloric  acid  is  noted. 

Syphilis  of  the  intestines  is  rare  and  its  recognition  before  death 
is  rarer.  Marked  diarrhea  which  will  not  yield  to  the  ordinary 
remedies,  the  stools  being  thin  and  watery  and  containing  blood 
and  pus,  may  be  noted.  Deep  palpitation  over  the  affected  portion 
of  the  intestinal  canal  will  elicit  pain.  Ulcerating  gummata  of 
the  intestines  may  lead  to  stenosis. 

Rectal  syphilis,  as  stated  above,  is  more  frequently  observed 
than  syphilis  of  other  portions  of  the  intestinal  canal.  Syphilis 
of  this  region  may  give  rise  to  no  symptoms  or  there  may  be  marked 
pain  on  defecation,  proctorrhea,  tenesmus,  incontinence  of  feces  or 
stricture. 

Diagnosis. — The  diagnosis  of  gastritis  occurring  early  in  the  course 
of  syphilis,  especially  in  the  absence  of  other  manifestations  of  the 
disease,  may  be  attended  with  the  utmost  difficulty.  If,  however, 
there  is  any  suspicion  that  the  condition  is  syphilitic,  and  when  the 
great  prevalence  of  syphilis  is  considered,  such  a  suspicion  should 
be  entertained  in  practically  all  cases  in  which  other  etiology  is 
not  evident,  a  Wassermann  test  should  be  performed,  which  if 
positive  would  indicate  antisyphilitic  treatment,  and  improvement 
of  the  gastric  symptoms  would  confirm  the  diagnosis. 

Gumma  of  the  stomach  may  be  mistaken  for  simple  ulcer  or  gastric 
carcinoma,  and  in  some  cases  a  positive  diagnosis  cannot  be  made. 
The  pain  of  ulcerating  gumma  is,  as  a  rule,  not  so  severe  or  regular 


272         SYPHILIS  OF   THE  GASTRO-INTESTINAL   TRACT 

as  that  observed  in  simyle  ulcer  and  is  not  so  dependent  upon  the 
ingestion  of  food.  Hemorrhage  also,  while  sometimes  noted,  does 
not  occur  as  often  as  in  simple  ulcer  and  is  not  so  severe.  Diminu- 
tion or  absence  of  hydrochloric  acid  is  the  rule  in  syphilis,  while  in 
simple  ulcer  hyperchlorhydria  is  more  frequent. 

In  gastric  carcinoma  the  development  of  the  condition  is  more 
rapid,  the  hemorrhage  is  more  frequent,  emaciation  more  marked 
and  pain  and  vomiting  more  constant  than  in  syphilis.  The  .T-ray 
picture  may  be  very  similar  in  both  conditions,  marked  deformity 
of  the  stomach  or  stenosis  of  the  pyloris  being  seen.  The  gastric 
analysis  is  also  very  similar  except  that  lactic  acid  is  not  so  fre- 
quently found  in  syphilis  as  in  carcinoma.  Finally,  the  diagnosis  of 
gastric  syphilis  must  rest  upon  laboratory  findings  and  therapeutic 
tests. 

The  diagnosis  of  syphilis  of  the  intestines  is  usually  most  difficult. 
Marked  diarrhea  which  does  not  yield  to  the  ordinary  remedies, 
with  thin  and  watery  stools  and  containing  blood  and  pus  should 
be  suspicious.  It  must,  however,  be  differentiated  from  amebic 
dysentery  and  the  diarrhea  of  'pellagra.  In  amebic  dysentery  the 
finding  of  the  Ameba  histolytica  and  in  pellagra  the  usual  presence 
of  other  manifestations  of  the  disease,  the  typical  eruption,  stoma- 
titis, etc.,  will,  as  a  rule,  serve  to  establish  a  diagnosis  of  these  con- 
ditions. A  positive  Wassermann  or  luetin  test  with  improvement 
of  the  symptoms  under  specific  therapy  will  confirm  the  diagnosis 
of  syphilis. 

Stenosis  of  the  intestine  due  to  syphilis  may  be  recognized  by 
the  a;-rays,  and  by  positive  laboratory  findings. 

Gumma  of  the  rectum  must  be  differentiated  from  carcinoma, 
and  may  usually  be  accomplished  by  the  history,  the  laboratory 
findings  (Wassermann-luetin  tissue  examination)  and  therapeutic 
tests. 

Prognosis. — The  prognosis  of  early  syphilitic  gastritis  is  good, 
as  under  specific  therapy  its  cure  is  usually  rapid.  * 

The  outlook  of  syphilitic  gummata  of  the  stomach  is  not  so  good, 
especially  if  located  at  the  pyloris  and  ulceration  has  taken  place, 
as  upon  healing,  more  or  less  cicatrization  will  take  place  and 
perhaps  stenosis. 

The  outcome  of  syphilis  of  the  intestines  is  similar  to  that  of 
syphilis  of  the  stomach  and  a  similar  prognosis  may  be  given. 

Treatment.^ — It  has  been  suggested  that  in  syphilis  of  the  stomach 
and  intestines  mercury  should  be  administered,  by  mouth  for  its 
local  effect  as  well  as  for  its  constitutional  effect.  If  this  is  done, 
mercury  should  also  be  administered  carefully  by  intramuscular 
or  intravenous  injection  and  salvarsan  intravenously.  Aside  from 
the  specific  medication  the  diet  should  be  regulated  according  to 


THE  STOMACH  AND  INTESTINES  273 

the  condition.  In  syphilitic  gastritis  the  diet  should  be  non- 
irritating  and  such  articles  of  food  as  cabbage,  smoked  meats, 
goose,  duck,  animal  fats,  acids,  pastries  and  cold  drinks  should  be 
forbidden. 

In  ulcerating  gumma  of  the  stomach  the  diet  should  also  be  non- 
irritating  and  the  food  should  leave  the  stomach  as  quickly  as 
possible.     It  should  consist  mainly  of  liquid  and  semisolid  articles. 

The  treatment  of  chancre  of  the  rectum  has  been  discussed  above. 
Rectal  gummata  may  be  treated  in  a  similar  manner. 


18 


CHAPTER  XIV. 

SYPHILIS  OF  THE  LIVER,  GALI^BLADDER,  SPLEEN 
AND  PANCREAS. 

THE  LIVER. 

Pathology. — Acute  yellow  atrophy  of  the  liver  has  been  observed 
during  the  course  of  syphiHs  and  considerable  controversy  has 
arisen  concerning  the  responsibility  of  the  Treponema  pallidum  in 
this  condition,  some  observers  contending  that  the  administration 
of  antisyphilitic  remedies  produces  the  condition  and  not  the  syphilis 
per  se.  But  as  Buschke^  has  shown  that  acute  yellow  atrophy  may 
develop  in  untreated  syphilitics,  and  that  the  condition  may  improve 
upon  the  institution  of  proper  therapy,  it  seems  that  there  is  little 
doubt  of  the  occasional  role  of  the  organism  of  syphilis  in  this 
condition. 

Syphilitic  cirrhosis  may  occur  in  association  with  gumma  of  the 
liver  or  independently.  The  liver  is  usually  smaller  than  normal 
when  gummata  are  not  present,  while  on  section  bands  of  sclerotic 
tissue  are  observed  between  the  lobules.  The  process  is  usually 
observed  in  a  more  or  less  limited  portion  of  the  liver  and  generally 
leads  to  necrosis  and  inflammatory  infiltration.  Microscopically 
the  cells  are  seen  to  be  necrotic  and  undergoing  fatty  degeneration 
and  amyloid  change  may  also  be  present. 

Gummata  of  the  liver  vary  in  size  from  1  or  2gpim.  to  immense 
tumors  which  may  be  mistaken  for  malignant  growths.  Cirrhosis 
is  generally  associated  with  this  condition.  The  microscopic  picture 
of  gummata  of  the  liver  does  not  differ  materially  from  gummata 
observed  elsewhere.    Treponemata  can  usually  be  demonstrated. 

Perihepatitis  may  occur  as  a  localized  condition  or  as  a  thickening 
of  the  entire  capsule  or  the  liver.  It  generally  follows  syphilitic 
involvement  in  the  liver  but  may  precede  it. 

Clinical  History. — Icterus  is  a  comparatively  frequent  symptom 
of  early  syphilis  and  occurs,  usually  developing  suddenly,  most 
frequently  about  the  sixth  week  following  the  infection.  Several 
theories  have  been  advanced  to  account  for  it.  It  has  been  thought 
to  be  due  to  enlargement  of  the  lymphatic  glands  of  the  portal 
vein,  to  a  catarrhal  condition  of  the  bile  duct,  to  duodenal  catarrh 
and  to  the  direct  action  of  the  treponemata   on  the  liver.     The 

1  Berl.  klin.  Wchnschr.,  1910,  Ixvii,  p.  238, 


THE  LIVER 


275 


latter  theory  is  probably  correct.  The  condition  may  or  may  not 
be  accompanied  by  enlargement  of  the  liver  with  pain  and  tender- 
ness. Fever  is  usually  present,  the  urine  contains  bile  and  the 
feces  are  more  or  less  clay-colored.  The  jaundice  may  disappear 
spontaneously  in  three  or  four  weeks  or  it  maj^  persist  for  months 
if  treatment  is  not  instituted. 

Acute  yelloio  atrophy  is  a  grave  and  always  fatal,  but  fortunately 
rare,  seciiiel  of  the  early  icterus  of  syphilis.  The  condition  may, 
however,  be  primary,  that  is,  other  symptoms  may  develop  before 
the  jaundice.  The  symptoms  are  the  same  as  those  noted  in  acute 
yellow  atrophy  due  to  other  causes,  namely,  headache,  tachycardia, 
insomnia,    "coffee    grounds"    vomit,    tarry    stools,    hemorrhages 


Fig.  57. — Treponema  pallida  iu  liver.     Levaditi's  stain. 


from  the  mucous  membranes,  and  into  the  skin,  convulsions,  coma 
and  death.  The  liver  diminishes  rapidly  in  size.  The  urine  is 
decreased  in  amount  and  contains  bile,  albumin,  casts,  mucin  and 
tyrosin. 

Cirrhosis  of  the  liver  due  to  syphilis  is,  as  a  rule,  a  late  manifes- 
tation, occurring  from  three  to  ten  or  more  years  after  infection 
and  is  not  infrequent.  The  symptoms  are  similar  to  those  seen  in 
non-luetic  cirrhosis.  Sometimes  the  first  symptom  noticed  is  an 
abnormal  "appetite  and  thirst.  This  may  be  followed  by  gastro- 
intestinal symptoms  such  as  pain  after  eating,  belching,  constipation, 
etc.  Jaundice  usually  occurs  early  and  may  be  very  marked.  The 
urine  is  scanty,  contains  bile  and  the  feces  are  generally  clay-colored. 
Vomiting  is  a  rather  frequent  symptom.    There  may  be  acites  and 


276  SYPHILIS  OF  THE  LIVER,  GALL-BLADDER 

pleural  effusion  sometimes  occurs.  More  or  less  cachexia  usually 
exists.  The  liver  may  be  either  atrophic  or  hypertrophic,  smooth 
or  nodular. 

Gummata  of  the  liver  will  produce  symptoms  varying  with  the 
size  of  the  tumors  and  their  location.  They  may  be  single  or 
multiple  and  if  located  on  the  surface  of  the  liver  usually  may  be 
palpated. 

Diagnosis. — The  icterus  occurring  early  in  the  course  of  syphilis 
is  usually  an  accompaniment  of  cutaneous  manifestations  and  may 
be  diagnosed  from  them  or  by  laboratory  procedures.  If  the 
icterus  occurs  as  the  only  symptom,  the  diagnosis  may  not  be  made, 
although  syphilis  should  be  thought  of  if  no  other  cause  of  the 
icterus  is  found.  Laboratory  procedures  will  in  the  majority  of 
such  cases  clear  up  the  diagnosis. 

Acute  yellow  atrophy  due  to  syphilis  must  be  diagnosed  from  the 
history,  the  presence  of  other  manifestations  of  syphilis,  laboratory 
procedures  and  postmortem  findings. 

The  differential  diagnosis  of  syphilitic  cirrhosis  from  that  due  to 
alcohol  may  be  exceedingly  difficult.  The  history,  the  presence  or 
absence  of  other  symptoms  or  lesions  of  syphilis,  the  Wassermann 
and  luetin  tests  and  therapeutic  procedures  may  enable  the  physician 
to  make  a  correct  diagnosis.  Howevel,  it  must  be  remembered  that 
syphilis  and  alcoholism  are  very  frequently  associated.  The 
Wassermann  test  on  the  acetic  fluid  has  been  found  positive  in 
these  conditions. 

Gummata  of  the  liver  may  resemble  carcinoma  and  present  some 
difficulty  of  diagnosis.  The  following  are  the  main  points  of 
differentiation : 


Gumma. 

Carcinoma. 

1. 

History  of  syphilis. 

1. 

None. 

2. 

Perhaps  presence  of    other  syphil- 

2. 

None. 

itic 

manifestations. 

3. 

Nodules  do  not  increase  much  in 

3. 

Nodules    increase   rapids 

size. 
4. 

Usually  no  pain. 

4. 

Pain  usually  present. 

5. 

Usually  spleen  enlarged. 

.5. 

Spleen  normal. 

6. 

Usually  in  middle  life  or  younger. 

6. 

Usually  past  middle  life. 

7. 

Little  cachexia. 

7. 

Marked  cachexia. 

8. 

Wassermann  or  luetin  usually  posi- 

8. 

Negative. 

tive. 

9. 

Improvement  under  specific  ther- 

9. 

No  improvement. 

apy. 

Prognosis. — The  prognosis  of  the  icterus  occurring  early  in  the 
course  of  the  disease  is  exceedingly  good,  as  it  usually  disappears 
spontaneously  in  three  or  four  weeks  even  without  treatment, 
while  under  specific  medication  it  clears  up  in  a  remarkable  manner. 


THE  SPLEEN  277 

Acute  yellow  atrophy  either  of  syphilitic  or  non-syphihtic  origin 
is  always  a  fatal  disease,  death,  as  a  rule,  taking  place  within  a 
week  or  ten  days  after  the  onset  of  symptoms. 

Syphilitic  cirrhosis  is,  as  a  rule,  of  grave  import,  although  under 
vigorous  antisyphilitic  treatment  improvement  or  even  cure  may 
be  noted.  The  same  may  be  said  of  gummata  of  the  liver,  although 
the  prognosis  of  this  condition  depends  to  a  large  extent  upon 
the  number,  the  size  and  location  of  the  gummata. 

Treatment. — The  early  icterus  of  syphilis  will  require  no  treatment 
but  specifics,  while  the  treatment  of  acute  yellow  atrophy  is  entirely 
symptomatic.  When  acites  or  pleural  effusion  occurs  in  cirrhosis 
of  the  liver  due  to  syphilis  the  fluids  should  be  removed  by  aspiration, 
otherwise  the  treatment  consists  of  specific  medication  and  general 
measures.  Rest  in  bed  should  be  insisted  upon.  Gummata  of  the 
liver  require  no  other  treatment  than  specific  and  general. 

THE  GALL-BLADDER. 

No  mention  of  syphilis  of  the  gall-bladder  in  the  acquired  form  of 
the  disease  can  be  found  in  the  literature.     (See  page  386.) 

THE  SPLEEN. 

Pathology. — Syphilitic  enlargement  of  the  spleen  is  quite  frequently 
noted  in  the  early  course  of  the  disease,  but  usually  the  organ  returns 
to  its  normal  size  upon  the  disappearance  of  the  more  acute 
symptoms. 

Diffuse  hyperplasia  of  the  spleen  later  in  the  course  of  syphilis 
with  thickening  of  the  reticulum  and  trabeculse  is  sometimes 
observed.    Amyloid  change  has  been  noted  in  cases  of  long  standing. 

Gummata  of  the  spleen  are  rather  rare  and  vary  markedly  in 
size  and  number.  Sometimes  being  miliary  and  very  numerous 
and  at  other  times  are  single  and  attain  a  size  which  render  them 
readily  palpable.  Treponemata  may  usually  be  demonstrated, 
especially  in  the  walls  of  the  arteries. 

Clinical  History. — Syphilitic  involvement  of  the  spleen  is  often 
accompanied  by  involvement  of  other  organs,  so  symptoms  referable 
to  this  organ  may  be  obscure.  It  usually  occurs  early,  sometimes 
before  the  syphilodermata  are  manifest,  and,  as  Wile  and  Elliott^ 
have  pointed  out,  probably  represents  the  earliest  visceropathy. 
The  spleen  may  be  markedly  enlarged,  palpable  and  sometimes 
movable.  Tenderness  may  or  may  not  be  noted  and  it  may  be  either 
hard  or  soft.  According  to  Osier  and  Gibson^  a  leukocytosis  sug- 
gestive of  leukemia  may  be  present. 

1  Am.  Jour.  Med.  Sc,  1915,  cl,  p.  512. 

2  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  iii,  p.  69. 


278  SYPHILIS  OF  THE  LIVER,   GALL-BLADDER 

Diagnosis. — There  is  nothing  in  the  symptomatology  of  syphiHs 
of  the  spleen  which  may  be  regarded  as  pathognomonic.  The 
diagnosis  of  the  involvement  of  this  organ  therefore  must  rest 
upon  indirect  evidence,  history,  other  manifestations  of  syphilis, 
laboratory  findings  and  therapeutic  tests. 

Prognosis. — The  prognosis  of  the  sj'philitic  involvement  of  the 
spleen  early  in  the  course  of  the  disease  is  good,  as  most  cases  readily 
return  to  normal  upon  the  institution  of  specific  treatment.  The 
outlook  of  the  later  syphilitic  disease  of  the  spleen  is  not  quite  so 
favorable. 

Treatment. — In  splenic  syphilis  no  other  treatment  than  specific 
and  general  is  indicated. 

THE  PANCREAS. 

Pathology. — Syphilis  of  the  pancreas  was  formerly  considered  a 
rare  condition,  but  Warthin  and  Wilson^  state  that  in  39  cases  of 
old  latent  syphilis  the  pancreas  was  not  found  normal  in  a  single 
one.  The  pathological  condition  found  was  an  interacinar  and 
interlobular  fibrosis  with  disappearance  of  the  islands  of  Langerhans 
through  fibrosis.  There  was  also  atrophy  with  compensatory 
hypertrophy,  regenerative  new  formation  of  acini,  and  infiltration 
of  lymphocytes  and  plasma  cells.  The  condition  is  said  by  these 
authors  to  be  essentially  a  "patchy"  one,  the  tail  and  body  of  the 
organ  being  more  frequently  involved  than  the  head,  except  in  the 
most  severe  cases  when  nearly  the  entire  gland  may  be  affected .  Tre- 
ponemata  were  found  in  the  active  inflammatory  areas  of  one  case. 

Gummata  of  the  pancreas  have  also  been  described. 

Clinical  History .^ — Syphilis  of  the  pancreas  certainly  is  rarely  recog- 
nized clinically.  The  symptoms  of  syphilitic  pancreatitis  are  epi- 
gastric pain,  tenderness,  fatty  diarrhea,  cachexia  and  glycosuria. 

Gummata  of  the  head  of  the  pancreas  may  cause  obstructive 
jaundice,  while  pressure  of  a  gumma  on  the  inferior  vena  cava  may 
produce  edema  of  the  lower  extremities.  Gummata  may  also  some- 
times be  palpated. 

Diagnosis. — The  diagnosis  of  syphilitic  pancreatitis  must  rest 
upon  the  symptoms  of  pancreatic  disease  as  outlined  above  as  well 
as  upon  the  histor}^,  other  manifestations  of  syphilis  or  positive 
laboratory  evidence  of  its  presence. 

Prognosis. — The  prognosis  of  syphilitic  pancreatitis  is  grave  but 
will  depend  upon  the  date  of  its  recognition  and  its  extent. 

Treatment.— The  treatment  of  syphilis  of  the  pancreas  aside  from 
the  specific  and  general  treatment  of  syphilis  consists  of  a  careful 
regulation  of  the  diet  (the  restriction  of  carbohydrates)  and  perhaps 
the  use  of  carbonated  waters  and  pancreatin. 

lAm.  Jour.  Med.  Sc,  1916,  clii,  p.  157. 


CHAPTER  XV. 

SYPHILIS  OF  THE  BREAST,  THYROID,  THYMUS, 
ADRENALS   AND   PITUITARY"  BODY. 

THE  BREAST. 

Pathology. — Chancre  of  the  breast  has  been  referred  to  in  Part  I 
in  the  chapter  on  Chnical  History.  Diffuse  syphilitic  infiltration 
and  circumscribed  gummata  have  also  been  observed,  the  former 
being  the  rarer  of  the  two  conditions.  They  are,  as  a  rule,  late 
manifestations  of  the  disease,  although  diffuse  infiltration  has  been 
noted  early  and  the  subcutaneous  tissue  as  well  as  the  glandular 
structure  may  be  attacked.  Gummata  may  be  single  but  usually 
are  multiple,  while  one  or  both  breasts  may  be  involved. 

Clinical  History. — Syphilitic  mastitis  may  cause  no  other  symptom 
than  swelling  of  the  gland  which  may  become  half  again  as  large 
as  normal  and  may  be  discovered  only  accidentally.  Pain  and 
tenderness  may  or  may  not  be  present  but  usually  are.  The  skin 
over  the  breast  usually  is  not  discolored,  but  is  smooth  and  the  gland 
is  hard  and  firm. 

Gummata  of  the  breast  occur  as  lumps  varying  greatly  in  size. 
As  a  rule  they  are  more  or  less  tender.  If  left  untreated  they  may 
break  down  and  ulcerate  through  the  skin,  and  upon  healing  form 
cicatrices,  the  skin  being  adherent  to  the  deeper  structures. 

Diagnosis. — Syphilitic  mastitis  must  be  differentiated  from 
mastitis  due  to  other  causes,  and  can  usually  be  accomplished  by 
the  history,  the  presence  of  other  syphilitic  manifestations,  positive 
laboratory  evidence  and  therapeutic  tests.  The  diagnosis  of 
gummata  before  ulceration  has  taken  place  will  also  depend  upon 
the  indirect  evidence  above  mentioned  or  the  tumor  may  be  removed 
for  microscopic  examination.  Ulcerating  gummata  may  be  mistaken 
for  carcinoma,  but  the  age  of  the  patient,  the  history,  and  laboratory 
tests  should  make  the  diagnosis  clear. 

Prognosis. — ^The  prognosis  of  diffuse  syphilitic  infiltration  of  the 
breast  is  probably  better  than  that  of  mastitis  due  to  other  causes 
as  it  usually  yields  to  specific  therapy.  Gummata  also,  as  a  rule, 
are  rather  amenable  to  treatment  although,  as  stated  above,  upon 
healing  cicatrices  may  form,  causing  adhesions  of  the  skin  to  the 
deeper  structures. 

Treatment. — No  treatment  but  specific  and  general  is  indicated 
in  syphilitic  mastitis.  Ulcerating  gummata  will  require  surgical 
dressings. 


280        SYPHILIS  OF  THE  BREAST,   THYROID,   THYMUS 

THE  THYROID  GLAND. 

Pathology. — Reimers^  is  said  to  have  observed  that  half  the 
cases  of  early  syphilis  show  enlargement  of  the  thyroid. 

Davis,2  in  1910,  reported  a  case  of  gumma  of  the  thyroid  and 
reviewed  the  literature,  finding  only  ten  other  cases  diagnosed 
histologically. 

Clinical  History. — Davis  states  that  gummata  of  the  thyroid  may 
cause  severe  dyspnea  by  pressure  on  the  trachea  and  by  inducing 
an  edema  of  the  larynx.  This  may  also  interfere  with  deglutition. 
Interference  with  the  function  of  the  thyroid  may  cause  myxedema. 
Symptoms  of  exophthalmic  goiter  also  may  occur.  The  nerve  trunks 
of  the  neck  may  be  involved,  causing  disturbance  of  their  functions. 
Gummata  of  small  size  may  cause  no  symptoms  but  the  enlargement. 

In  Davis's  own  case  the  patient  gave  a  history  of  syphilis  five  years 
previous  to  admission  to  the  hospital.  At  the  time  of  admission  the 
patient  complained  of  hoarseness,  great  inspiratory  dyspnea  and 
pain  on  swallowing.  This  condition  had  lasted  for  four  months 
with  frequent  exacerbations  in  which  the  dyspnea  was  so  great  that 
the  patient  became  cyanosed.  Tracheotomy  was  performed  eight 
days  after  admission  but  without  relief,  death  following  twelve 
hours  later. 

Diagnosis. — The  diagnosis  of  syphilis  of  the  thyroid  can  only  be 
made  by  the  history,  evidences  of  syphilis  of  other  regions,  labora- 
tory findings,  including  histological  examination,  and  therapeutic 
tests. 

Prognosis. — As  stated  above  Davis's  patient  died  twelve  hours 
after  tracheotomy.  Of  the  seven  other  cases  of  gummata  of  the 
thyroid  in  acquired  syphilis  which  were  confirmed  by  histological 
examination  and  reviewed  by  Davis,  three  died  and  four  recovered 
under  specific  medication,  while  eight  cases  reviewed  by  Davis 
which  were  diagnosed  only  clinically  recovered  under  specific 
treatment. 

Treatment. — The  treatment  of  syphilis  of  the  thyroid,  aside  from 
specific  and  general  measures,  is  symptomatic.  Tracheotomy  may 
be  necessary  on  account  of  the  dyspnea. 

THE  THYMUS  GLAND. 

Syphilis  of  the  thymus  is  an  exceedingly  rare  condition,  especially 
in  the  acquired  form  of  the  disease.  The  condition  as  it  occurs  in 
congenital  syphilis  will  be  described  in  Part  III. 

1  Osier  and  Gibson:  In  Power  and  Murphy's  System  of  Syphilis,  London,  1909, 
iii,  p.  14. 

2  Arch.  Int.  Med.,  1910,  v,  p.  47. 


THE  PITUITARY  BODY  281 

THE  ADRENALS. 

Involvement  of  the  adrenals  is  rare  in  acquired  syphilis.  However, 
patients  dying  of  Addison's  disease  are  sometimes  found  to  have 
gummata  of  these  glands.  Sezary^  has  reported  a  case  in  which 
some  of  the  symptoms  of  Addison's  syndrome  were  observed  and 
in  which  at  autopsy  numerous  treponemata  were  found  in  the 
cortex  of  the  adrenals.  The  author  has  seen  a  case  of  Addison's 
disease  in  which  a  definite  history  of  syphilis  and  a  four-plus  Wasser- 
mann  reaction  were  obtained.  Syphilitic  involvement  of  the 
adrenals  without  the  symptoms  of  Addison's  disease  cannot  be 
diagnosed  clinically,  although  syphilis  of  the  adrenals  might  well 
be  suspected  in  cases  of  Addison's  disease  and  laboratory  procedures 
instituted  to  determine  its  presence. 

Addison's  disease,  whether  of  syphilitic  etiology  or  not,  is  always 
a  fatal  disease,  so  treatment  would  be  of  no  avail,  and  should  there- 
fore be  symptomatic. 

THE  PITUITARY  BODY. 

Syphilis  of  the  hypophysis  is  an  exceedingly  rare  condition. 
Hektoen,2  in  1896,  reviewed  the  literature  and  reported  a  gumma 
of  this  body. 

Gushing^  reports  a  case  in  which  there  had  been  polyuria,  poly- 
dipsia and  glycosuria,  although  no  acetone  bodies  were  present. 
The  diagnosis  of  diabetis  mellitus  was  made,  and  under  diabetic 
diet  the  patient  improved.  Less  than  a  year  later  the  condition 
recurred  with  intense  frontal  headache,  vertigo,  and  vomiting.  The 
patient  then  became  very  drowsy,  irrational  and  disoriented; 
developed  Cheyne-Stokes  respiration,  projectile  vomiting,  thick 
speech,  static  ataxia,  tremor,  incoordination  of  movements,  etc., 
and  died.  The  necropsy  revealed  a  syphiloma,  large  enough  to  be 
distinctly  seen  by  the  naked  eye  on  section,  involving  the  anterior 
and  intermediate  lobes  of  the  pituitary  body. 

The  diagnosis  of  syphilis  of  the  hypophysis  would  be  extremely 
difficult  during  life. 

Cases  of  glycosuria,  especially  if  the  acetone  bodies  are  not 
present,  should  perhaps  be  looked  upon  with  suspicion  and  a 
Wassermann  test  made.  In  cases  of  glycosuria  in  which  the  Was- 
sermann  is  positive  it  might  be  well  to  institute  specific  treatment. 
In  certain  cases  of  acromegaly,  gigantism  and  infantilism  a  Wasser- 
mann test  might  be  of  service. 

1  Gaz.  d.  Hop.,  1914,  Ixxxvii,  p.  1317. 

2  Tr.  Chicago  Path.  Soc,  1897,  ii,  p.  129. 

3  The  Pituitary  Body  and  its  Disorders,  Philadelphia  and  London,  1912,  p.  263. 


CHAPTER  XVI. 
SYPHILIS  OF  THE  GENITO-URINARY  ORGANS. 

THE  PENIS. 

Syphilitic  affections  of  the  mucous  membrane  of  the  penis, 
have  been  described  in  Part  I  in  the  chapter  on  CHnical  History. 
The  body  of  the  penis  may  also  be  the  seat  of  gummata,  and  sj^ihihtic 
inflammation  of  the  corpora  cavernosum  has  been  described. 

Gummata  of  the  body  of  the  penis  may  be  single  or  multiple  and 
vary  from  one  or  two  millimeters  to  one  centimeter  or  more  in 
diameter.  They  are  usually  painless  and  may  be  discovered  acci- 
dentally. They  may  soften  and  ulcerate  either  into  the  urethra 
or  on  the  surface. 

The  diagnosis  is,  as  a  rule,  easy  as  gummata  of  this  region  are 
scarcely  to  be  mistaken  for  any  other  condition,  especially  if  labora- 
tory tests  are  applied. 

Gummata  of  the  body  of  the  penis  if  recognized  early  usually 
will  disappear  under  specific  therapy  without  leaving  any  serious 
after-effects.  If,  however,  an  early  diagnosis  is  not  made  and 
vigorous  treatment  instituted,  ulceration  may  take  place  either 
into  the  urethra  or  onto  the  surface  which  upon  healing  will  form 
cicatrices  and  more  or  less  deformity.  Sometimes  the  process 
is  so  extensive  as  to  destroy  the  entire  penis. 

THE  TESTICLE. 

Pathology. — Syphilis  of  the  testicle  occurs  in  two  forms,  as  a 
diffuse  orchitis  or  epididj^mitis  or  gummata.  In  either  case  the 
process  usually  begins  in  the  testicle  and  later  involves  the 
epididymus.  Diffuse  syphilitic  orchitis  presents  on  section  delicate 
bands  of  connective  tissue  of  a  whitish  color  and  extending  from  the 
rete  to  the  tunica  albuginea.  Microscopically,  the  intertubular 
stroma  is  seen  to  contain  a  few  leukocytes  and  is  greatly  thickened 
by  the  deposit  of  new  connective  tissue,  while  a,trophy  and  hyaline 
change  are  seen  in  the  tubules.  Hypertrophy  of  the  endothelium 
of  the  arteries  is  also  observed.  Gummata  of  the  testicle  occur  as 
firm  nodules  enclosed  in  fibrous  tissue.  These  may  coalesce,  forming 
a  large  mass  which  may  break  down  and  ulcerate.    (See  Fig.  58.) 


THE  TESTICLE 


283 


Clinical  History. — Syphilis  of  the  testicle  is  of  frequent  occurrence 
and  may  be  found  as  early  as  two  or  three  months  after  infection 
although,  as  a  rule,  it  is  a  late  manifestation.  The  diffuse  syphilitic 
orchitis  causes  a  swelling  of  the  gland  which  is  usually  uniform  and 
painless  but  may  be  tender.  The  development  of  the  condition  is 
slow  and  may  only  be  recognized  accidentally.  The  epididymis  may 
or  may  not  be  involved.  If  it  is  involved,  it  is  usually  secondary. 
Hydrocele  is  sometimes  observed. 


Fig.  58. — Gumma  of  testicle. 


Gummata  of  the  testicle  also  give  rise  to  little  or  no  pain.  These 
tumors  vary  in  size  from  two  or  three  millimeters  to  several  centi- 
meters. While  the  condition  is  usually  unilateral  it  may  be  bilateral. 
There  will  be  diminution  in  the  sexual  desire  and  even  complete 
impotence,  depending  upon  the  extent  of  the  lesion. 

Diagnosis. — Diffuse  syphilitic  orchitis  must  be  differentiated  from 
traumatic  orchitis,  and  from  gonorrheal  orchitis.  In  traumatic 
orchitis  there  is  history  of  injury,  and  the  development  of  the  swelling 
is  rapid  with  pain,  tenderness  and  redness  of  the  skin.  Gonorrheal 
orchitis  usually  is  to  be  distinguished  by  the  history  of  recent 
gonorrheal  urethritis  or  its  presence,  by  the  more  acute  course,  or 
by  the  complement-fixation  test  for  gonorrhea  and  the  Wassermann 
test  and  by  therapeutic  procedures. 

Gummata  of  the  testicle  may  be  mistaken  for  tuberculosis  or 
carcinoma.  Tuberculosis  is  more  frequently  found  in  the  epididymis, 
is  more  often  associated  with  suppuration,  causes  more  cachexia, 
and  tubercle  bacilli  may  be  found  in  the  discharge.    However,  the 


284  SYPHILIS  OF   THE  GEN  I  TO-URINARY  ORGANS 

diagnosis  may  have  to  rest  upon  laboratory  evidence  and  thera- 
peutic tests.  In  carcinoma  there  is  enlargement  of  the  lymph  glands, 
and  section  of  the  growth  will  show  the  typical  picture  of  carcinoma, 
while  in  gumma  of  the  testicle  there  is  usually  no  lymphatic  enlarge- 
ment, sections  will  not  show  the  picture  of  carcinoma  and  syphilitic 
laboratory  tests  will  generally  be  positive.  Furthermore,  upon 
the  administration  of  specific  remedies  there  will  usually  be  improve- 
ment of  the  condition. 

Prognosis. — The  prognosis  of  the  healing  of  syphilitic  involvement 
of  the  testicle  is  good  but  the  prognosis  of  the  function  of  the  organs 
depends  upon  the  extent  and  severity  of  the  process. 

Treatment. — Syphilis  of  the  testicle  as  a  rule  needs  no  special 
treatment  other  than  wearing  a  suspensory  bandage.  If  hydrocele 
exists,  the  fluid  should  be  removed  by  aspiration.  Ulcerating  gum- 
mata  should  be  treated  antiseptically  and  if  the  involvement  is 
very  extensive  it  may  be  necessary  to  remove  the  testicle. 

THE  PROSTATE. 

Pathology. — Syphilitic  prostatitis  is  a  most  rare  condition.  Cook^ 
in  1912  reported  a  case  of  gumma  of  the  prostate  and  reviewed  the 
literature,  finding  mention  of  but  six  cases.  Rush^  in  1913  reported 
an  additional  case. 

Clinical  History. — The  symptoms  of  syphilis  of  this  gland  are 
similar  to  those  observed  in  non-luetic  prostatitis  and  depend  upon 
the  extent  of  the  condition. 

In  Cook's  case  there  was  painful  urination,  sensation  of  fulness 
in  the  perineum,  becoming  painful  on  defecation,  if  constipated, 
and  following  coitus,  slight,  thin,  sticky,  brownish  discharge, 
increased  on  pressure  of  prostate  which  was  enlarged  so  that  the 
size  could  not  be  determined,  and  of  the  consistency  of  a  hard 
rubber  ball. 

Diagnosis. — Syphilitic  involvement  of  the  prostate  must  be 
differentiated  from  simple  hypertrophy,  gonorrheal  prostatitis 
and  carcinoma,  and  should  be  accomplished  by  the  history,  the 
presence  of  other  syphilitic  manifestations,  laboratory  procedures 
and  specific  therapy. 

Prognosis. — Syphilis  of  the  prostate  is  so  rare  that  little  data 
as  to  its  prognosis  are  available.  In  Cook's  case  a  very  greatly 
enlarged  prostate  returned  to  normal  size  after  the  administration 
of  specific  remedies. 

Treatment. — ^Aside  from  the  general  and  specific  treatment  of 
syphilis  of  the  prostate,  light  prostatic  massage  may  be  of  benefit 
and  in  case  of  suppuration  prostatectomy  may  be  advisable. 

1  Interstate  Med.  Jour.,  1912,  xix,  p.  980. 

2  Med.  Rec,  1913,  Ixxxiv,  p.  1028. 


THE  CERVIX  285 

THE  SEMINAL  VESICLES. 

Power^  states  that  no  trustworthy  evidence  of  syphihtic  involve- 
ment of  these  organs  has  been  recorded. 

THE  VAGINA. 

Chancre  of  the  vagina  has  been  discussed  in  Part  I  in  the  chapter 
on  CHnical  History.  That  the  vagina  may  be  the  seat  of  the 
syphilomycodermata  has  also  been  pointed  out.  Gellhorn  and 
Ehrenfest"  in  an  exhaustive  monograph  on  syphilis  of  the  internal 
genitals  of  the  female  state  that  these  lesions  are  very  rare  in  the 
vagina,  but  do  occur  hi  the  macular,  papular  and  gummatous 
types.  The  macular  eruption  is  the  most  rare  and  may  occur 
either  as  isolated  reddivsh  spots  or  as  a  diffuse  eruption.  The  papular 
syphilomycoderm  is  more  frequently  seen  in  the  vagina  than  the 
macular.  Both  the  eroded  and  ulcerative  forms  of  the  papular 
eruption  have  been  observed  and  do  not  differ  from  these  lesions 
seen  elsewhere.  According  to  the  above-mentioned  authors  Oppen- 
heim  states  that  the  hypertrophic  or  vegetating  papular  lesion  is 
excessively  rare  in  the  vagina.  The  gummatous  syphilomycoderm, 
according  to  Gellhorn  and  Ehrenfest,  is  very  rarely  seen  in  the 
vagina  except  as  a  continuation  of  a  gumma  from  adjacent  regions. 
It  is  sometimes  seen,  however,  as  an  ulcer  which  may  lead  to 
fistulse  and  strictures.  None  of  the  syphilomycodermata  of  the 
vagina  presents  characteristic  symptoms  and  therefore  these  lesions 
are  only  recognized  by  examination  with  a  speculum. 

THE  CERVIX. 

Chancre  of  the  cervix  has  been  described  in  Part  I.  According 
to  Gellhorn  and  Ehrenfest  it  is  the  most  frequent  of  all  the  syphilitic 
lesions  of  the  internal  genitalia  in  the  female. 

The  other  syphilitic  lesions  observed  on  the  cervix  consist  of 
macular,  papular  and  gummatous  syphilomycodermata.  The  first 
two  types  have  been  but  infrequently  described.  Gellhorn  and 
Ehrenfest  in  their  monograph  have  added  eight  cases  to  the 
literature. 

According  to  these  authors  the  macular  eruption  occurs  as  small 
circular  areas  which  become  eroded.  They  may  be  single  or  multiple 
and  several  may  coalesce,  forming  larger  areas.  Treponemata  are 
very  abundant,  which  accounts  for  their  great  infectivity. 

The  papular  lesion  which  is  more  common  usually  consists  of  very 

1  System  of  Syphilis,  London,  1909,  ii,  p.  145. 

2  Am.  Jour.  Obst.,  1916,  Ixxiii,  p.  864. 


286  SYPHILIS  OF   THE  GENITO-URINARY  ORGANS 

small  elevations,  but  large  papules  may  occur  through  the  blending 
of  several  smaller  ones.  These  lesions  rarely  develop  into  the 
vegetating  type  but  the  more  frequent  sequel  is  an  ulceration. 
Gellhorn  and  Ehrenfest  state  that  these  ulcerations  show  a  char- 
acteristic color  which  is  not  found  in  any  non-specific  affections. 
This  color  consists  of  a  yellow  or  whitish  yellow  which  is  obviously 
due  to  fatty  degeneration  of  the  superficial  cell  layers.  An  undertone 
of  red  or  pink  is  observed  in  the  yellow  and  is  distributed  as  dots  or 
fine  lines  which  is  thought  to  represent  many  newly  formed  and 
dilated  capillaries. 

The  macular  and  papular  lesions  which  have  not  ulcerated  give 
rise  to  no  distinctive  symptoms  but  when  ulceration  has  taken  place 
there  is  usually  a  profuse  yellowish  discharge. 

The  gummatous  syphilomycoderm  occurring  on  the  cervix  is 
more  common  than  the  other  types.  These  lesions  usually  ulcerate 
and  may  extend  to  the  vagina  or  into  the  cervical  canal.  The  usual 
color  is  a  yellow  but  it  may  vary  from  whitish  or  dirty  gray  to  a 
dark  red  or  purple.  There  is  usually  no  pain  but  bleeding  and  a 
yellowish  discharge  are  common. 

Gellhorn  and  Ehrenfest  mention  the  following  characteristic 
features  of  the  syphilomycodermata  of  the  cervix: 

1.  Specific  ulcers,  as  a  rule,  produce  very  little  secretion;  only 
extensive  tertiary  ulcers  or  necrotic  gummata  cause  a  pathological 
discharge. 

2.  There  is  no  pain  either  spontaneous  or  on  touch, 

3.  Luetic  lesions  are  frequently  at  some  distance  from  the  external 
OS,  which  hardly  ever  occurs  in  non-specific  ulcerations  of  the  cervix. 

4.  Syphilitic  ulcers  are  characterized  by  their  sharp  outline. 

5.  Syphilitic  ulcers  are  usually  covered  with  a  film-like  deposit 
which  may  be  wiped  off  easily  and  exhibits  a  characteristic  fatty 
luster. 

6.  Syphilitic  ulcers  show  very  little  if  any  inflammatory  reaction 
of  the  surrounding  mucosa. 

Diagnosis. — In  making  a  diagnosis  of  chancre  of  the  cervix  an 
examination  should  be  made  for  treponemata.  If  they  are  not  found, 
the  Wassermann  test  should  be  performed  at  frequent  intervals 
(every  two  or  three  days)  until  positive  or  until  it  is  certain  the 
condition  is  not  syphilitic. 

The  diagnosis  of  the  macular  and  papular  lesions  is  generally 
easy  owing  to  the  usual  presence  of  other  manifestations  of  the 
disease  such  as  syphilodermata,  and  the  Wassermann  is  usually 
positive. 

The  diagnosis  of  the  gummatous  lesions  is  not  always  so  easy,  as 
there  may  not  be  other  manifestations  of  the  disease  and  the 
Wassermann  may  be  negative.     The  provocative  Wassermann  in 


THE   UTERUS  287 

such  cases  is  of  value,  while  the  removal  of  a  portion  of  the  growth 
for  microscopic  examination  and  the  results  of  specific  therapy 
should  clinch  the  diagnosis. 

The  gummatous  lesion  of  the  cervix  may  resemble  carcinoma,  as 
in  one  of  the  cases  reported  by  Gellhorn  and  Ehrenfest,  in  which  a 
cauliflower  growth  the  size  of  a  child's  fist  and  occupying  the 
entire  cervix  was  observed.  This  was  differentiated  from  carcinoma 
only  by  microscopic  examination,  as  the  Wassermann  was  negative 
and  in  spite  of  specific  therapy  the  patient  died  from  malignant 
syphilis. 

Treatment. — No  other  treatment  than  specific  and  palliative  is 
indicated  in  syphilis  of  the  cervix,  as  ordinarily  these  lesions  are 
amenable  to  proper  therapy. 

THE  UTERUS. 

Although  chancre  of  the  endometrium  has  not  been  observed 
it  is  conceded  as  possible  for  the  treponemata  to  enter  at  the  cervical 
canal  and  a  chancre  develop  on  this  tissue.  Gellhorn  and  Ehrenfest 
state  that  no  conclusive  evidence  of  involvement  of  the  endometrium 
in  the  so-called  secondary  stage  of  the  disease  has  been  published, 
although  Franceschini  agrees  with  Chearleoni,  Fasola,  and  others 
who  claim  that  leucorrhea,  uterine  neuralgia  and  dysmenorrhea 
may  be  produced  by  such  lesions. 

An  endometritis  occurring  late  in  the  course  of  the  disease  and 
depending  upon  a  gummatous  condition  of  the  endometrium  has 
been  described  by  numerous  writers.  Marshall^  states  that  in  endo- 
metritis due  to  ulcerating  gummata  there  is  a  mucopurulent  dis- 
charge and  hemorrhage.  This  writer,  however,  does  not  mention 
any  personal  observations  nor  does  he  quote  from  the  observations 
of  others.  Gellhorn  and  Ehrenfest^  have  pointed  out  that  the  only 
well-authenticated  case  of  gummatous  endometritis  described  in  the 
literature  was  reported  by  Hoffmann. 

In  this  case  the  patient  was  admitted  to  the  hospital  with  chronic 
sepsis  two  months  following  the  delivery  of  living  twins.  She  died 
four  weeks  later  and  at  autopsy  the  entire  surface  of  the  endome- 
trium was  involved  with  gummatous  tissue  several  centimeters  in 
thickness  and  extending  deeply  into  the  myometrium. 

Gummata  of  the  myometrium  have  been  described  by  several 
writers,  but  Gellhorn  and  Ehrenfest  after  a  critical  review  of  all  of 
the  available  reported  cases  reach  the  conclusion  that  the  evidence 
is  not  sufficient  "  on  which  to  base  the  pathology  of  this  condition  or 
to  attempt  a  classification  of  its  various  types."     These  authors 

1  Syphilology  and  Venereal  Diseases,  New  York,  1906,  p.  180. 

2  Am.  Jour.  Obst.,  1916,  Ixxiii,  p.  864. 


288  SYPHILIS  OF   THE  GENITO-URINARY  ORGANS 

further  state  that  there  is  even  a  greater  paucity  of  facts  concerning 
the  "characteristic  sclerosis"  of  the  myometrium.  Letulle  is  quoted 
as  having  found  a  typical  endophlebitis  in  the  veins  of  the  sub- 
mucosa,  while  Morisani  found  an  endarteritis.  All  other  cases  are 
based  upon  improvement  of  irregular  hemorrhages  under  antiluetic 
treatment. 

THE  FALLOPIAN  TUBES. 

That  the  Fallopian  tubes  may  be  the  seat  of  the  syphilitic  process 
is  within  the  range  of  possibility,  but  Gellhorn  and  Ehrenfest  con- 
sider that  none  of  the  cases  so  far  reported  will  bear  the  scrutiny  of 
modern  knowledge.  Even  the  case  of  Bouchard  and  Lepine,  which 
is  quoted  by  all  writers  on  the  subject,  they  consider  as  not  con- 
clusive. In  this  case  both  tubes  of  a  woman,  aged  forty  years,  were 
found  at  autopsy  to  be  thickened  to  the  size  of  the  finger  with  oblit- 
eration of  the  lumen.  On  section  three  gummata  the  size  of  a  hazel- 
nut, soft  and  of  a  reddish  color,  were  found  in  each  tube.  Micro- 
scopic examination  of  sections  were  made  and  described,  but  the 
description  does  not  correspond  to  the  findings  considered  character- 
istic by  modern  observers.  The  diagnosis  is  based  upon  similar 
tumors  found  in  the  liver  and  brain  and  a  rarefying  osteitis  of  the 
right  clavicle.  «; 

THE  OVARIES. 

Numerous  writers  have  described  both  the  pathology  and  clinical 
history  of  syphilitic  oophoritis.  The  work  of  Lancereaux^  is  prob- 
ably most  frequently  quoted.  This  writer  describes  two  cases.  The 
first  case  is  that  of  a  woman,  aged  thirty-three  years,  who  was 
admitted  to  the  hospital  with  manifestations  of  syphilis  of  the 
nervous  system  and  a  history  of  syphilis  ten  years  previously.  At 
autopsy  adhesions  were  found  between  the  uterus,  ovary,  and  the 
surrounding  parts.  One  of  the  ovaries  contained  a  white  induration 
which  occurred  in  patches.  In  the  other  case  the  diagnosis  of  gumma 
of  the  ovaries  was  made  from  the  fact  that  two  tumors  the  size  of  an 
egg  were  found  in  the  region  of  the  ovaries,  which  rapidly  decreased 
in  size  under  potassium  iodide.  Marshall^  states  that  the  symptoms 
of  syphilitic  gvaritis  are  not  distinctive,  apart  from  other  signs  of 
syphilis.  He  continues  that  there  may  be  pain  and  tenderness  in 
the  region  of  the  ovary,  but  that  the  chief  sign  is  menorrhagia  in  the 
earlier  stages,  followed  by  intermittent  metrorrhagia. 

Gellhorn  and  Ehrenfest,^  after  critically  reviewing  all  of  the  avail- 
able literature,  reach  the  following  conclusions : 

1  Traite  de  la  Syphilis,  Paris,  1868,  i.  p.  286. 

2  Syphilology  and  Venereal  Disease,  New  York,  1906,  p.  180. 

3  Am.  Jour.  Obst.,  1916,  Ixxiii,  p.  864. 


THE   URETHRA  289 

"Various  changes  in  the  ovaries  (simple  enlargement,  syphilitic 
oophoritis,  tertiary  sclerosis  of  the  ovary,  ovarian  gumma)  have 
been  described  as  typical  expressions  of  the  secondary  and  tertiary 
stages  of  luetic  infection,  but  in  no  instance  (with  the  possible  ex- 
ception of  Hoffmann's  case^)  has  positive  proof  been  furnished  that 
such  alterations  are  actually  due  to  a  local  luetic  process. 

The  fact  that  in  some  syphilitic  patients  an  amenorrhea  or,  more 
commonly,  a  metrorrhagia  disappears  after  specific  medication,  can- 
not be  accepted  as  evidence  of  a  syphilitic  ovarian  lesion.  Spiro- 
chseta  have  as  yet  not  been  demonstrated  in  the  ovaries  of  adults." 


THE  URETHRA. 

Chancre  of  the  urethra  has  been  discussed  in  Part  I  in  the  chapter 
on  Clinical  History.  The  urethra  is  also  occasionally  the  seat  of 
gummata. 

Dey  and  Kirby-Smith,^  in  1915,  reported  two  cases  and  reviewed 
the  literature.    In  both  of  their  cases  ulceration  was  observed. 

Gumma  of  the  urethra  may  occur  either  primarily  or  as  an  ex- 
tension from  the  corpora  cavernosa.  There  is  more  or  less  enlarge- 
ment of  the  penis  while  ulceration  is  usually  present  and  a  thin 
serosanguinolent  discharge  is  found.  If  this  condition  remains 
untreated,  a  fistula  may  be  formed  or  it  may  become  phagedenic. 

Gumma  of  the  urethra  must  be  differentiated  from  gonorrheal 
urethritis  and  chancre  of  the  urethra.  In  the  former  condition  the 
discharge  is  more  purulent  and  contains  gonococci,  while  in  the 
latter  condition  there  will  be  history  of  exposure,  and  probably 
inguinal  adenitis,  instead  of  a  history  of  other  manifestations  of 
syphilis  and  probably  no  adenitis.  The  Wassermann  or  luetin  tests 
are  more  frequently  positive  in  gumma  than  in  chancre  and  of  course 
are  negative  in  gonorrhea. 

If  seen  before  marked  ulceration  has  taken  place,  gummata  of  the 
urethra  usually  disappear  under  specific  medication.  If,  however, 
ulceration  or  phagedena  has  occurred  it  may  be  most  refractory, 
and  even  upon  healing  marked  deformity  may  result. 

Treatment. — Ordinarily  no  other  treatment  than  specific  and 
general  is  indicated,  but  if  ulceration  is  marked  injections  of  bichlo- 
ride of  mercury  (1  to  4000)  may  be  used,  and  if  fistula  or  phagedena 
exist,  surgical  dressings  should  be  applied. 

1  This  is  the  case  quoted  under  syphilis  of  the  endometrium  in  which  in  addition 
to  the  gummatous  endometritis  the  right  tube  and  ovary  were  transformed  into  a 
gummatous  mass. 

2  South.  Med.  Jour.,  1913,  vi,  p.  20. 

19 


290  SYPHILIS  OF   THE  GENITO-URINARY  ORGANS 

THE  BLADDER. 

Syphilis  of  the  bladder  is  apparently  exceedingly  rare.  Simons^ 
reported  a  case  of  probable  syphilitic  ulcer  of  the  bladder.  In  this 
case  hypogastric  pain,  dull  and  dragging  in  character,  at  first  inter- 
mittent but  later  continuous,  was  noted.  The  pain  was  increased 
when  the  bladder  was  even  moderately  distended  with  urine,  so  that 
urine  was  voided  about  every  hour  during  the  day  and  five  or  six 
times  at  night.  The  urine  was  clear,  amber,  acid,  and  without 
sediment,  except  a  moderate  number  of  white  cells.  Cystoscopy 
revealed  in  the  region  just  behind  the  trigone  several  round  ulcers 
with  clear-cut  edges  and  about  twice  the  size  of  tl\e  normal  ureteral 
orifice.  The  right  ureteral  orifice  was  irregular,  due  to  the  proximity 
of  a  large,  irregular,  ulcerated  patch  adjoining  it  on  its  lateral  aspect. 
Just  mesial  to  the  right  ureteral  orifice  and  in  the  trigone  a  very  small 
reddened  spot,  resembling  a  tubercle  that  had  not  ulcerated,  was 
seen.  After  passing  from  observation,  six  weeks  later,  there  was  a 
marked  exacerbation  of  the  condition,  especially  the  hypogastric 
pain,  while  the  urine  showed  both  red  and  white  blood  cells.  At 
this  time  cystoscopy  revealed  the  entire  trigone  and  a  small  part  of 
the  post-trigone  region  raw,  angry,  red,  and  markedly  injected,  but 
with  no  distinct  ulcerations  present. 

Diagnosis. — The  diagnosis  of  syphilis  of  the  bladder  can  only  be 
made  by  the  symptoms  of  bladder  disturbance,  urinalysis,  cysto- 
scopy, the  history  of  syphilis,  or  the  presence  of  other  manifestations 
of  the  disease,  positivejaboratory  tests  and  the  improvement  of  the 
condition  under  specific  therapy. 

Prognosis. — The  prognosis  should,  as  a  rule,  be  good  if  recognized 
before  the  process  has  progressed  too  far.  The  great  danger  is  the 
perforation  of  the  bladder  wall  by  ulceration.  In  Simons's  case 
complete  apparent  recovery,  both  symptomatically  and  anatom- 
ically, followed  specific  medication. 

Treatment. — ^The  treatment  of  syphilis  of  the  bladder  should  con- 
sist of  vigorous  specific  treatment  with  rest  in  bed.  Irrigations  with 
bichloride  solution  (1  to  4000)  should  be  employed.  Syphilitic  ulcers 
which  do  not  readily  heal  under  specific  medication  and  irrigations 
might  be  touched  with  silver  nitrate  by  means  of  an  operating 
cystoscope. 

THE  URETER. 

According  to  Osier  and  Gibson,^  Hadden  has  described  an  un- 
doubted case  of  syphilitic  involvement  of  the  ureter.  Most  other 
syphilographers  are  silent  on  the  subject. 

1  Jour.  Am.  Med.  Assn.,  1913,  Ix,  p.  1943. 

2  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  iii,  p.  79. 


THE  KIDNEY  291 


THE  KIDNEY. 


Pathology. — All  types  of  nephritis  with  syphilis  as  the  cause,  as 
well  as  gummata  of  the  kidney,  have  been  described.  During  the 
early  course  of  the  disease,  especially  when  the  cutaneous  lesions 
are  most  manifest,  disease  of  the  kidney  is  of  quite  frequent  occur- 
rence. This,  however,  is  usually  rather  mild  in  character,  being  in 
all  probability  due  to  the  toxins  generated  and  not  to  the  trepone- 
mata  per  se.  However,  acute  and  chronic  nephritis  may  develop, 
and  while  there  is  nothing  distinctive  of  syphilis  in  the  anatomical 
picture,  and  treponemata  have  not  been  demonstrated  in  the  kid- 
neys in  acquired  syphilis,  there  seems  no  doubt  but  that  the  con- 
dition is,  sometimes  at  least,  directly  due  to  the  action  of  these 
organisms. 

Amyloid  kidney  is  also  sometimes  observed  as  a  consequence  of 
syphilis. 

Gummata  of  the  kidney,  while  exceedingly  rare,  do  occur  and 
vary  in  size  from  1  or  2  mms.  to  1  cm.  or  more.  They  are  usually 
multiple,  and  appear  as  pale  yellow  nodules.  Bowlby^  has  reported 
a  case  of  diffuse  gummatous  infiltration. 

Clinical  History. — Disease  of  the  kidney  occurring  early  in  the 
course  of  syphilis  is  manifest  by  small  amounts  of  albumin  and  a 
few  hyaline  and  granular  casts,  and  is  usually  mild  in  character.  It 
may,  however,  become  severe  in  type  and  present  the  clinical  picture 
of  acute  nephritis,  developing  suddenly,  usually  with  severe  pains  in 
the  lumbar  region,  anorexia,  fever,  and  perhaps  nausea  and  vomit- 
ing. There  is  more  or  less  edema  of  the  face,  legs,  and  scrotum. 
The  urine  is  scanty,  highly  colored,  of  a  low  specific  gravity,  and 
contains  enormous  quantities  of  albumin  (in  one  personal  case  32 
grams  per  liter),  and  many  tube  casts  of  various  kinds.  In  the  most 
severe  cases  there  may  be  anuria  and  early  development  of  coma. 

Munk'  has  recently  described  a  type  of  syphilitic  kidney  disease 
which  he  considers  more  degenerative  than  inflammatory,  occurring 
early  in  the  course  of  the  disease  and  more  frequently  in  women 
than  in  men.  It  is  characterized  by  a  marked  anemia,  more  or  less 
edema,  malaise  and  weakness,  dyspnea,  occasional  headache,  rarely 
vomiting,  and  little  or  no  fever.  The  urine  is  decreased  in  amount, 
the  twenty-four-hour  quantity  varying  from  300  to  1200  c.c.  It  is, 
however,  normal  in  color  and  reaction,  but  with  high  specific  gravity, 
and  an  albumin  content  as  high  as  2.8  per  cent.  Microscopically,  a 
few  red  cells,  many  white  cells,  cylindrical  epithelium,  and  hyaline 
casts  are  seen.  However,  the  feature  to  which  Munk  particularly 
calls  attention  is  the  presence  of  lipoids  observed  as  fine  droplets  or 

1  Tr.  Path.  Soc,  London,  1897,  xlciii,  p.  128. 

2  Dermat.  Ztschr.,  1914,  xxi,  p.  591. 


292  SYPHILIS  OF   THE  GEN  I  TO-URINARY  ORGANS 

in  packets,  either  in  the  epithehal  cells  or  in  the  casts,  which  are 
doubl}^  refractive  through  a  Nicols  polariscope.  Under  the  ordinary 
microscope  these  droplets  resemble  neutral  fat  globules,  but  when 
examined  with  the  polariscope  show  a  dark  central  cross  separating 
four  bright  peripheral  quadrants.  While  Munk  found  these  lipoids 
in  the  urine  of  several  nephritics  of  non-1  uetic  origin  they  were  more 
abundant  in  syphilitic  nephritis. 

Stengel  and  Austin^  have  reported  similar  findings,  and  in  experi- 
mental uranium  nephritis  in  rabbits  and  chromate  nephritis  in  a 
dog  secured  negative  results. 

Chronic  nephritis  is  of  comparatively  infrequent,  occurrence  and 
is  usually  seen  from  three  to  ten  years  following  the  syphilitic 
infection.  It  may,  however,  occur  earlier.  In  one  case  seen  by  the 
author  albumin  was  found  in  the  urine  eighteen  months  following 
the  appearance  of  the  chancre.  The  symptoms  will  depend  upon 
whether  interstitial  or  parenchymatous  nephritis  exists.  In  the 
former  case  it  is  characterized  by  polyuria,  small  amounts  of  al- 
bumin, few  hyaline  casts,  little  or  no  edema,  but  high  blood-pressure. 
In  parenchymatous  nephritis  the  urine  is  scanty,  of  high  specific 
gravity,  contains  more  or  less  albumin,  and  usually  many  hyaline 
and  granular  casts.  There  is  usually  edema,  and  the  blood-pressure 
is  increased. 

Amyloid  kidney  is  also  of  late  occurrence  in  syphilis,  and  is  char- 
acterized by  a  large  amount  of  albumin  in  the  urine,  which  is  usually 
diminished  in  quantity,  but  may  be  increased.  There  is  generally 
more  or  less  anemia  and  edema  of  the  face  and  legs.  The  blood- 
pressure  is  normal  or  low. 

Gummata  of  the  kidney  occur  late  in  the  course  of  the  disease  and 
will  cause  symptoms  depending  upon  their  size  and  location.  They 
may  sometimes  cause  symptoms  resembling  renal  calculus.  Occa- 
sionally they  develop  to  such  a  size  that  they  are  palpable. 

Diagnosis. — Acute  syphilitic  nephritis  is  to  be  distinguished  from 
acute  nephritis  of  other  etiology,  according  to  Osier  and  Gibson,^ 
first,  by  the  fact  that  the  amount  of  urine  in  syphilitic  nephritis  is 
not  lessened  to  the  same  extent  as  in  other  forms  with  the  same 
amount  of  albumin;  second,  in  proportion  to  the  amount  of  albumin 
casts  are  rare;  third,  the  general  type  of  the  disease  affects  the 
patient,  as  a  rule,  less  than  the  other  types.  To  these  features, 
however,  must  be  added  the  history  of  syphilis  or  other  evidence 
of  it,  positive  laboratory  findings,  and  in  some  cases  improvement 
with  specific  treatment. 

The  diagnosis  of  chronic  syijhilitic  7iephritis  may  be  most  difficult 
but  it  seems  to  the  author  that  if  all  nephritics  were  examined  for 

1  Am.  Jour.  Med.  Sc,  1915,  cvlix,  p.  12. 

2  Power  and  Murphy:  System  of  Syphilis,  London,  1908,  iii,  p.  74. 


THE  KIDNEY  293 

syphilis,  both  chnically  and  by  laboratory  methods,  more  cases  of 
syphilitic  nephritis  would  be  found.  Of  course  other  evidences  of 
syphilis  and  positive  laboratory  tests  would  not  be  absolute  proof 
that  the  nephritis  was  luetic,  but  the  improvement  of  the  condition 
under  carefully  administered  specifics  would  be  strong  presumptive 
evidence  that  such  is  the  case. 

Gummata  of  the  kidney  must  be  distinguished  from  malignancy 
and  from  renal  calculus.  A  diagnosis  of  malignancy  of  the  kidney 
has  been  made  on  the  clinical  findings  and  operation  performed, 
when  the  true  nature  of  the  condition  was  found  to  be  syphilitic. 
Such  mistakes  in  the  majority  of  cases  at  least,  would  not  occur  if 
all  patients  with  kidney  tumors  were  subjected  to  careful  laboratory 
tests  for  syphilis. 

Renal  calculus  can  usually  be  recognized  by  the  a"-rays. 

Prognosis. — The  early  involvement  of  the  kidney  by  the  syphilitic 
process  when  but  a  small  amount  of  albumin  and  few  casts  are 
present,  as  a  rule,  readily  yields  to  specific  therapy.  However,  when 
the  process  assumes  an  acute  type  with  all  the  symptoms  of  acute 
nephritis  the  outlook  must  be  considered  most  grave.  Other  forms 
of  syphilis  of  the  kidney  (chronic  nephritis,  amyloid  kidney,  gum- 
mata) present  a  more  favorable  outlook,  although,  as  with  syphilis 
of  the  heart,  the  prognosis  should  be  reserved  until  the  effect  of 
antisyphilitic  medication  be  noted. 

Treatment. — As  with  syphilis  of  the  heart  so  with  kidney  syphilis, 
the  treatment  should  be  twofold,  that  is,  directed  toward  the  syphilis 
and  toward  the  kidney  condition.  In  the  slight  nephritis  occurring 
early  in  the  course  of  syphilis  speciJ&cs  and  general  treatment  alone 
are  indicated.  Specifics,  however,  must  be  administered  with  extreme 
caution  in  all  nephritic  conditions;  the  urine  being  examined  for 
albumin  and  casts  as  well  as  the  phenolsulphonephthalein  test 
performed  at  frequent  intervals. 

In  the  more  severe  types  of  syphilitic  nephritis  rest  in  bed  is 
imperative.  Diuretics,  such  as  digitalis  and  potassium  citrate,  as 
well  as  cathartics,  should  be  administered.  Hot  packs  to  promote 
diaphoresis  should  be  applied,  especially  in  acute  cases.  The  diet 
should  be  nourishing,  and  consist  largely  of  carbohydrates. 


CHAPTER  XVII. 

SYPHILIS  OF  THE  BONES,  JOINTS,  BURSiE, 
TENDONS  AND  MUSCLES. 

THE   BONES. 

Pathology. — Syphilitic  involvement  of  the  bones  consists  of 
periostitis,  osteitis  and  osteomyelitis. 

Periostitis  may  either  be  localized  or  diffuse.  In  the  localized 
variety  the  process  may  extend  inward  and  involve  the  bone  proper 
or  outward,  forming  an  ulcer  of  the  skin.  In  the  diffuse  variety  of 
periostitis,  which  is  a  rarer  condition,  considerable  swelling  is  seen, 
although  it  is  usually  greater  at  one  end.  The  periostium  may 
separate  from  the  bones,  and  spicules  of  bone  may  be  formed  from 
the  ossifying  periostium.  The  process  begins  with  a  hyperemia 
followed  by  a  swelling  consisting  of  a  network  of  new  connective- 
tissue  fibers  with  an  infiltration  of  lymphocytes.  As  the  connective 
tissue  arises  from  osteal  cells  a  certain  number  are  differentiated 
into  bone  cells  and  osteophytes  are  formed. 

Gummatous  involvement  of  the  periosteum  may  occur  but  it 
usually  is  followed  by  extension  to  the  bone  itself. 

Osteitis  occurs  either  in  circumscribed  localities  or  may  be  diffuse, 
affecting  the  entire  bone.  At  first  there  is  usually  a  thickening  or 
sclerosis  of  the  bone  which  may  continue  as  such  but  generally 
absorption  takes  place  and  there  is  not  only  loss  of  the  new  formed 
osseous  deposits  but  also  of  the  sound  bone.  The  Haversian  canals 
become  enlarged  by  the  absorption  of  the  bony  tissue  around  them, 
and  adjacent  canals  may  unite  forming  irregular  spaces.  The 
process  may  progress  until  large  portions  of  the  bone  are  destroyed. 
At  times  the  sclerotic  condition  persists  and  the  bone  becomes 
exceedingly  hard,  resembling  ivory.  The  process  of  infiltration 
may  take  place  on  the  surface  of  the  bone  beneath  the  periosteum 
when  outgrowths  or  exostoses  are  formed.  When  the  process 
encroaches  on  the  bloodvessels  cutting  off  the  blood  supply  necrosis 
results. 

Gummatous  involvement  of  bone  proper  takes  place  as  foci 
varying  in  size  from  1  mm.  to  1  or  2  cm.  If  the  gummata  are  not 
very  large,  complete  absorption  may  take  place.  However,  if  absorp- 
tion is  incomplete,  a  portion  of  the  gumma  may  remain  as  a  caseous 
mass  and  the  process  may  extend  as  an  osteitis,  causing  more  or 


THE  BONES 


295 


less  destruction  of  bone.  As  a  result  of  the  osteitis  the  bone  may 
become  very  fragile  and  fractures  result  from  light  trauma  or  even 
muscular  contraction. 

Osteomyelitis. — When  the  syphilitic  process  first  invades  the 
medulla  of  the  bones  the  term  osteomyelitis  is  applied.  This  is 
usually  in  the  form  of  a  gummatous  process,  and  the  gummata 
may  become  encapsulated  and  bony  tumors  result  or  they  may 
break  down  and  either  perforate  the  bone  proper  or  find  an  outlet 
through  the  joint.  The  process  may  be  extensive,  causing  a  thick- 
ening of  the  entire  bone,  or  it  may  be  confined  to  a  single  small 
gumma. 


Fig.  59. — Extensive  osteitis  of  bones  of  skull. 


The  bones  may  be  attacked  by  the  Treponema  pallidum  as  an 
extension  from  the  soft  tissues,  from  gummata  of  the  skin  or  mucous 
membranes  or  with  the  bones  of  the  skull  from  meningeal  in- 
volvement. 

Clinical  History. — While  it  is  usually  stated  that  the  bones  which 
are  nearest  the  surface  of  the  body  are  most  frequently  attacked 
by  syphilis  and  although  lesions  of  these  bones  are  more  easily 
recognized  clinically,  since  the  introduction  of  the  .r-rays  it  has 
been  observed  that  other  bones  are  rather  frequently  involved. 


293 


SYPHILIS  OF  THE  BONES,  JOINTS,   BURS^ 


Periostitis  may  occur  very  early  in  the  course  of  the  disease, 
according  to  Swediaur  as  quoted  by  Townsend/  as  early  as  the 
fifth  day  following  the  appearance  of  the  chancre,  but  it  usually 


Fig.  60. 


-Syphilitic  periostitis  and  osteitis  of  cranial,  bones  showing  numerous 
points  of  absorption. 


makes  its  appearance  between  the  sixth  and  ninth  months  and  is 
often  much  later.     Periostitis  is  undoubtedly  the  cause  of  the  so-, 
called  osteocopic  pains  which  occur  early  in  the  course  of  syphilis 
often  before  the  appearance  of  the  skin  lesions.     These  pains  are, 


1  Morrow:  System    of    Genito-urinary    Diseases,    Syphilology    and    Dermatology, 
New  York,  1898,  ii,  p.  274. 


THE  BONES 


297 


as  a  rule,  nocturnal  and  are  more  frequently  found  in  women  than 
in  men.  Often  there  are  no  objective  symptoms,  although  when 
the  periostitis  is  severe  and  localized  there  will  be  a  more  or  less 
elastic  swelling  having  no  very  definite  shape.  The  skin  may  be 
somewhat  reddened  and  movable  when  superficial  bones  are 
attacked.  When  the  process  extends  outward  the  skin  may  be 
involved  and  an  ulcer  produced. 


Fig.  61. — Osteitis  of  humeri. 


Osteitis  and  osteomyelitis  usually  occur  between  the  second  and 
third  years  following  the  chancre  but  the  gummatous  type  may 
appear  much  later.  The  symptoms  accompanying  osteitis  and 
osteomyelitis  depend  upon  the  severity  of  the  process  and  consist 
of  aching  pains,  tenderness,  swelling  and  symptoms  especially 
associated  with  the  bone  affected.  Thus  if  one  of  the  long  bones  of 
the  lower  limb  be  involved,  limping  will  be  observed,  or  there  may 
be  simply  a  sense  of  heaviness  in  the  limb.  If  exostoses  are  formed, 
they  may  often  be  visible  as  nodules  under  the  skin  or  they  may  be 
palpable.  The  rarefication  of  the  bone  may  lead  to  spontaneous 
fracture  as  mentioned  above. 


298 


SYPHILIS  OF   THE  BONES,   JOINTS,   BURSM 


When  the  bones  of  the  skull  are  the  seat  of  the  syphilitic  process 
the  periosteum  is  usually  first  attacked  and  subsequently  either  the 
internal  or  external  table  or  both  may  become  affected.  When  the 
bone  substance  is  involved  there  may  be  more  or  less  loss  of  sub- 


FiG.  62. — Syphilitic  osteoperiostitis  of  ulna  (note  slight  involvement  of  radius). 


stance.  Occasionally  this  occurs  in  the  form  of  rings  or  semicircles 
suggestive  of  the  annular  papular  syphiloderm.  Syphilis  of  the 
bones  of  the  skull  will  cause  headache,  and  tender  spots  can  gener- 
ally be  found.     Often  there  will  be  considerable  bulging  and  the 


THE  BONES  299 

process  may  extend  inward,  causing  compression  of  the  brain  with 
severe  headache  and  other  marked  symptoms  depending  upon  the 
location. 

The  usual  outcome  of  syphilitic  involvement  of  the  bones  of  the 
face  is  degeneration  and  loss  of  substance,  and  often  most  gruesome 
appearances  result  from  destruction  of  these  bones.  The  so-called 
saddle  nose  is  not  infrequently  the  result  of  this  involvement. 
(Fig.  63). 


Fig.  63. — Saddle  nose. 

The  sternum  is  very  frequently  the  seat  of  exostoses,  as  are  the 
long  bones,  especially  the  tibia,  but  they  present  no  unusual  features. 

Syphilis  of  the  ribs  may  cause  severe  pain  which  may  simulate 
pleurisy  or  intercostal  neuralgia. 

The  vertebrae  are  rarely  attacked  by  the  syphilitic  process. 
Hunt,^  in  1914,  stated  that  only  100  authentic  cases,  of  which  4 
were  his,  had  been  reported  up  to  that  time.  Whitney  and  Baldwin,^ 
in  1915,  in  100  unselected  cases  of  undoubted  syphilis  found  3 
cases  of  gumma  of  the  spine.  The  process  is  most  frequently  found 
in  the  cervical  region,  though  it  may  occur  in  any  portion  of  the 
spinal  column.  All  types  of  syphilitic  bone  involvement  are  found. 
The  symptoms  are  pain,  tenderness,  rigidity,  and  deformity. 

It  is  sometimes  possible  to  palpate  exostoses,  especially  in  the 
cervical  region  and  the  process  may  be  revealed  by  the  .r-rays. 

1  Am.  Jour.  Med.  Sc,  1914,  cxlviii,  p.  164. 

2  Jour.  Am.  Med.  Assn.,  1915,  Ixv,  p.  1989. 


300 


SYPHILIS  OF   THE  BONES,  JOINTS,   BURSM 


When  the  bones  of  the  fingers  and  toes  are  attacked  by  periostitis 
or  osteomyehtis  the  term  syphilitic  dactylitis  is  appHed.  The  term 
is  also  used  to  designate  syphiUtic  involvement  of  the  subcutaneous 
connective  tissue  and  the  fibrous  structures  of  the  joints  of  the 
fingers.  The  onset  of  the  condition  is  usually  slow  and  is  first 
observed  as  a  swelling  of  the  affected  member.     One  or  more  of 


Fig.  64. — Syphilitic  osteitis  with  necrosis  of  superior  maxillary,  hard  palate,  and 

tubinates. 


the  digits  may  be  attacked,  the  fingers  being  more  frequently  the 
seat  of  the  process  than  the  toes,  and  usually  the  joints  sooner  or 
later  become  involved.  The  condition  may  persist  for  a  considerable 
length  of  time  and  finally  be  absorbed  or  the  gummatous  deposit 
may  become  soft  and  be  discharged  through  a  sinus.  The  bone  may 
be  left  shortened  or  lengthened  or  it  may  resume  its  normal  size. 


THE  BONES  301 

If  necrosis  occurs,  there  will  be  more  or  less  deformity.  As  with 
affections  of  the  bones  in  general  syphilitic  dactylitis  is  usually  a 
comparatively  late  manifestation,  occurring,  as  a  rule,  from  five  to 
fifteen  years  after  the  chancre,  but  it  has  been  noted  as  early  as 
the  second  year. 

Diagnosis. — The  so-called  osteocopic  pains  which  occur  early  in 
the  course  of  syphilis  and  which  are  undoubtedly  due  to  invasion 
of  the  periosteum  by  the  Treponema  pallidum  may  be  mistaken  for 
rheumatism  or  neuralgia.  The  usual  presence  of  other  manifesta- 
tions of  syphilis  or  of  positive  laboratory  evidence  will  make  the 
diagnosis  easy  in  most  cases.  When  these  are  lacking  the  fact 
that  the  pain  generally  is  worse  at  night  will  be  suspicious,  but  this 
would  scarcely  be  sufficient  for  a  positive  diagnosis. 

The  later  diffuse  periostitis  may  be  mistaken  for  sarcoma,  but  an 
.T-ray  plate  will  reveal  the  fact  that  the  bone  is  uniformly  enlarged 
throughout  its  entire  circumference,  while  in  sarcoma  the  enlarge- 
ment is  on  one  side  only. 

Osteitis  and  periostitis  of  syphilitic  origin  must  be  distinguished 
from  non-syphilitic  conditions. 

Tnherculosis  is  a  more  destructive  process  than  syphilis  and  rarely 
attacks  the  shaft  of  the  bone.  It  is  also  characterized  by  wasting 
of  the  muscles  in  the  vicinity  of  the  affected  bone,  is  more  painful, 
and  shows  less  thickening  of  the  periosteum  than  syphilis,  although 
there  may  be  considerable  edema  of  the  connective  tissue.  The 
.r-ray  picture  is  also  hazy  with  loss  of  bone  detail. 

Carcinoma  is,  as  a  rule,  secondary  to  soft  tissue  involvement 
elsewhere,  is  essentially  a  destructive  process  and  most  frequently 
attacks  the  ends  of  the  long  bones. 

Osteitis  deformans,  as  well  as  syphilis,  shows  a  thickened  cortex 
and  bowing.  The  .r-ray  revels  that  the  entire  shaft  is  involved  in 
the  former  condition. 

Suppurative  osteomyelitis  is  accompanied  by  more  or  less  fever 
and  leukocytosis  and  the  pain  is  not  more  severe  at  night  as  it 
usually  is  with  syphilis.  The  .r-rays  show  the  process  of  destruction 
and  repair  going  on  at  the  same  time,  with  thickened  new  bone 
which  is  irregular  in  outline  and  may  contain  areas  of  much  lessened 
density. 

The  pain  of  syphilis  of  the  ribs  may  simulate  pleurisy  or  intercostal 
neuralgia.  Pleurisy  may  be  differentiated  by  the  cough,  fever  and 
the  physical  signs.  The  use  of  the  a:-rays  may  reveal  the  nature  of 
the  process,  although  it  usually  is  necessary  to  resort  to  laboratory 
procedures. 

Syphilitic  dactylitis,  as  a  rule,  presents  little  difficulty  of  diagnosis. 
The  ;r-rays  show  in  the  earlier  stages  that  the  condition  is  confined 
to  the  shaft  of  the  bone,  although  later  the  epiphyses  may  be 


302  SYPHILIS  OF  THE  BONES,   JOINTS,   BURSM 

involved.  The  differentiation  from  tuberculosis  is  usually  easy  in 
that  the  syphilitic  process  appears  to  veil  the  bone  with  several 
layers  of  periosteal  overgrowth,  while  in  tuberculosis  the  medullary 
portion  is  involved  and  a  necrotic  area  formed. 

Finally  it  must  be  said  that  the  diagnosis  of  syphilis  of  the  bone 
should  rest  more  upon  the  history,  the  presence  or  absence  of  con- 
comitant syphilitic  lesions  and  the  laboratory  findings,  than  upon 
the  clinical  evidence  found  in  the  bones  themselves.  It  must  be 
admitted,  however,  that  the  Wassermann  reaction  is  sometimes 
negative  in  well-marked  cases  of  bone  syphilis,  and  the  diagnosis 
may  have  to  rest  on  the  time-honored  therapeutic  test. 

Prognosis. — The  prognosis  of  syphilitic  bone  disease  depends 
entirely  upon  the  location  and  extent  of  the  process.  The  perios- 
titis occurring  early  in  the  course  of  syphilis  is  usually  very  amenable 
to  treatment. 

Osteitis  and  osteomyelitis  also,  as  a  rule,  yield  to  specifics,  although 
if  exostoses  are  formed  their  absorption,  as  a  rule,  will  not  occur. 
The  best  that  can  be  hoped  for  is  to  stop  the  process. 

Syphilis  of  the  bones  of  the  skull  is  to  be  looked  upon  with  grave 
concern,  owing  to  the  danger  of  extension  of  the  process  to  the 
meninges.  However,  if  diagnosed  in  time  such  involvement  should 
yield  to  antisyphilitic  treatment. 

As  stated  above  when  the  bones  of  the  face  are  attacked  there 
is  usually  marked  degeneration  and  loss  of  substance.  Naturally 
the  best  possible  outcome  of  such  a  condition  is  the  stopping  of 
the  process. 

Syphilitic  involvement  of  the  vertebrae  is  of  grave  import,  owing 
to  the  danger  of  extension  to  the  meninges  of  the  cord.  However, 
if  the  condition  is  diagnosed  before  the  process  has  become  very 
extensive  the  prognosis  should  be  good,  and  complete  recovery 
should  occur  under  vigorous  antisyphilitic  treatment. 

Dactylitis  due  to  syphilis,  in  the  majority  of  cases  even  after 
the  process  has  existed  for  some  time,  is  peculiarly  amenable  to 
specifics. 

Treatment. — The  treatment  of  syphilis  of  the  bones,  if  recognized 
before  ulceration  through  the  skin  or  mucous  membrane  occurs, 
usually  need  consist  of  nothing  but  specific  and  general  measures. 
The  so-called  osteocopic  pains  due  to  periostitis  early  in  the  course 
of  the  disease  have  been  found  to  yield  remarkably  to  potassium 
iodide.  The  pain  of  the  later  periostitis,  osteitis  and  osteomyelitis 
may  be  so  severe  that  surgical  interference  is  indicated.  The  perios- 
teum should  be  incised,  or  if  this  does  not  suffice,  the  bone  should 
be  trephined.  If  suppuration  of  a  gumma  of  bone  has  occurred 
and  an  abscess  formed,  it  should  be  freely  opened,  curetted  and 
treated  with  antiseptic  solution. 


THE  JOINTS  303 

Spontaneous  fractures  and  separation  of  the  epiphysis  from  the 
diaphysis  should  be  treated  as  any  other  fracture,  although  union 
sometimes  is  most  difficult  to  obtain.  When  necrosis  of  bone  has 
occurred  and  sequestra  have  formed  they  should  be  removed  with 
great  care  and  antiseptic  solutions  used. 

If  exostoses  are  formed  which  press  upon  important  structures 
and  they  do  not  decrease  in  size  under  specific  therapy,  they  should 
be  removed. 

When  the  syphilitic  process  attacks  the  outer  table  of  the  bones 
of  the  skull  and  necrosis  has  occurred,  the  diseased  portion  should 
be  removed.  If  evidence  goes  to  show  that  the  inner  table  is  affected 
and  the  meninges  are  not  involved,  the  diseased  portion  of  bone 
should  be  allowed  to  remain  as  long  as  possible  so  that  the  dura 
mater  may  become  thickened  and  thus  become  better  able  to  take 
the  place  of  the  bone.  Following  the  healing  of  the  lesion  the 
diseased  portion  of  bone  may  be  replaced  by  a  silver  plate  or  a 
leather  cover  may  be  worn. 

When  the  bones  of  the  face  are  attacked  and  sloughing  occurs, 
as  it  usually  does,  the  diseased  portions  of  bone  should  be  removed. 
Great  care  should,  however,  be  exercised  that  the  process  does  not 
extend  to  the  meninges.  Following  the  removal  of  the  bone  the 
parts  should  be  thoroughly  irrigated  with  an  antiseptic  solution 
and  dressings  applied.  After  healing  certain  of  the  deformities 
such  as  saddle  nose  may  be  at  least  partially  overcome  by  plastic 
surgery.  This  consists  of  the  use  of  inert  substances  such  as  wood, 
metal,  rubber  and  paraffin,  or  the  use  of  living  tissues,  bone  from 
some  other  portion  of  the  patient's  body,  such  as  parts  of  the  tibia, 
bone  from  some  other  individual  and  animal  bone. 

Syphilis  of  the  vertebral  column  will  require  special  treatment 
depending  upon  its  extent.  Such  appliances  as  plaster  jackets 
and  similar  supports  may  be  indicated. 

Syphilitic  dactylitis,  as  a  rule,  needs  no  other  treatment  than 
specific  and  general.  An  incision  is  rarely  justifiable,  although  if 
softening  occurs  and  a  sinus  is  formed,  the  diseased  bone  should  be 
removed  and  the  part  dressed  antiseptically. 

THE    JOINTS. 

Pathology. — That  the  joints  of  the  body  may  be  aft'ected  by 
syphilis  was  maintained  by  Peter  Martyr  as  early  as  1498.  The 
condition  was  denied  by  Hunter,  and  Ricord,  while  admitting  that 
the  joints  of  syphilitics  were  sometimes  diseased,  considered  the 
process  a  complication.    Richef^  was,  however,  the  first  accurately 

1  Memoires  de  I'Acad.  de  med.,  Paris,  1853,  xvii,  p.  249. 


304 


SYPHILIS  OF   THE  BONES,   JOINTS,   BURSM 


to  describe  luetic  joint  disease  and  termed  it  syphilitic  white  swell- 
ing. Since  his  time  numerous  syphilographers  have  written  of  joint 
infections,  and  several  varieties  have  been  described. 

Simple  arthralgia  in  which  little  or  no  pathological  change  is 
observed  has  been  described  by  most  investigators.  This  condition 
will  be  dealt  with  more  fully  in  the  section  on  Clinical  History. 


Fig.  65. — Syphilitic  arthritis  of  ankle-joint. 


Acute  synovitis  may  occur  comparatively  early  in  the  course  of 
the  disease,  usually  within  the  first  or  second  year.  The  synovial 
membrane  is  thickened  and  the  tissues  surrounding  the  joint  are 
more  or  less  edematous. 

Chronic  synovitis  may  follow  the  acute  form  or  it  may  develop 
some  years  later.  In  this  condition  there  is  considerable  swelling 
of  the  joint  due  to  effusion,  in  fact  a  chronic  hydrarthrosis  exists. 

Gummatous  affections  of  the  joints  may  occur  secondarily  to  such 
conditions  of  the  bones  as  mentioned  above  and  an  osteo-arthritis 
result  or  the  gummata  may  originate  in  the  synovial  membrane. 
The  infiltration  occurs  in  the  tissues  beneath  the  endothelium  of 


THE  JOINTS 


305 


the  synovial  membrane  and  is  usually  diffuse  but  may  occur  as 
small  nodules.  The  cartilages  of  the  joint  and  the  bones  usually 
remain  unaffected,  however,  the  syphilitic  process  may  spread  to 
the  surrounding  tissues. 

Charcot's  joint  is  a  condition  observed  late  in  the  course  of  syphilis, 
either  with  tabes  dorsalis  or  as  a  precursor  of  that  malady.  The 
capsule  of  the  joint  is  dilated,  often  ruptured  and  may  be  entirely 
destroyed.  The  synovial  membrane  is  rough,  thick  and  often 
adherent  to  the  surrounding  parts.  In  old  cases  it  may  be  absent. 
The  synovial  fluid  is  usually  thin  and  clear  but  may  rarely  be  bloody 
or  purulent.  At  first  it  is  found  in  large  quantity  escaping  through 
the  ruptured  capsule  and  infiltrating  the  surrounding  tissues, 
causing  considerable  swelling.      Particles  of  bone  and  detritis  are 


Charcot  joint.     (Jelliffe  and  White.) 


often  floating  in  it.  There  is  either  erosion  of  the  ends  of  the  bones 
and  joint  surfaces  with  considerable  reduction  in  their  size,  or 
more  rarely,  hypertrophy. 

Clinical  History. — Syphilis  of  the  joints  certainly  is  more  frequent 
than  it  formerly  was  considered.  Whitney^  found  involvement  of 
the  joints  in  15.2  per  cent,  of  544  syphilitics. 

Simph  arthralgia,  referred  to  above,  in  which  little  or  no  patho- 
logical change  can  be  demonstrated  in  the  joint  occurs  rather  early 
in  the  course  of  syphilis,  often  before  any  cutaneous  lesions  are 
manifest,  but  is  more  frequently  seen  as  an  accompaniment  of  those 
lesions.  The  pain  has  been  described  as  resembling  the  so-called 
"growing  pains"  of  the  young  and  may  be  worse  at  night.    One  or 


1  Jour.  Am.  Med.  Assn.,  1915,  Ixv,  p.  1986. 


20 


306  SYPHILIS  OF   THE  BONES,  JOINTS,   BURSM 

more  joints  may  be  affected  and  the  condition  is  prone  to  disappear 
without  treatment  and  often  recurs. 

Acute  synovitis,  as  stated  above,  may  occur  comparatively  early 
in  the  course  of  syphilis,  usually  within  the  first  or  second  year. 
There  is  generally  pain  on  either  marked  flexion  or  extension  of 
the  joint,  although  motion  within  certain  limits  may  be  painless. 
The  joint  is  swollen  and  local  heat  is  observed.  There  is  occasion- 
ally redness  of  the  skin  over  the  joint  and  fluctuation  may  be  demon- 
strated.' Usually  more  than  one  joint  is  involved  and  the  large 
ones,  knee,  shoulder,  elbow,  wrist  or  rarely  the  hip  are  most  fre- 
quently the  seat  of  the  process.  The  condition  generally  lasts  one 
or  two  weeks  and  is  followed  by  a  return  to  normal  or  by  a  chronic 
synovitis. 

Chronic  Synovitis. — In  this  condition  there  is  generally  marked 
swelling  with  effusion,  and  fluctuation.  Little  pain  is  present  while 
movement  is  not  greatly  impaired.  The  knee  is  the  most  frequently 
affected  joint  and  the  process  is  usually  bilateral.  The  condition 
may  last  for  months,  and  if  complete  resolution  does  not  occur 
ankylosis  may  result. 

Guvimatovs  affections  of  the  joints  are  found  late  in  the  course 
of  the  disease.  The  symptoms  will  depend  upon  the  extent  of  the 
involvement.  Pain  may  or  may  not  be  intense  and  even  in  quite 
severe  cases  movement  may  be  little  hindered.  There  is  usually 
more  or  less  effusion.  The  knee  is  also  the  most  frequently  affected 
joint  in  this  condition,  but  contrary  to  the  chronic  synovitis  the 
process  is  generally  unilateral.  Whitney  and  Baldwin^  have  pointed 
out  the  frequency  of  involvement  of  the  joints  of  the  spine  in 
syphilis.  These  investigators  found  of  100  unselected  syphilitics 
only  26  with  perfectly  normal  spines,  6  more  were  considered  as 
doubtful.  Of  the  remaining  68  cases  all  but  4  had  a  type  of  spinal 
abnormality  which  is  considered  more  or  less  •  characteristic  of 
syphilis. 

The  synovia  of  the  spinal  joints  is  attacked  which  at  first  causes 
loss  of  motion  from  spasm  but  later,  as  the  process  becomes  less 
acute,  motion  is  limited  by  the  formation  of  adhesions  and  even 
complete  fixation  occurs.  These  adhesions  are  unaffected  by  anti- 
syphilitic  treatment  but  may  be  broken  up  by  forcible  manipula- 
tion. There  is  usually  a  characteristic  deformity,  whether  the 
condition  is  due  to  spasm  or  adhesions.  This  is  either  a  slight 
prominence  of  the  spines,  a  flattened  area  or  a  shallow  depression, 
and  depends  upon  the  location  of  the  involvement.  However, 
it  is  suggested  that  a  second  factor  may  be  operative,  namely,  that 
if  the  intervertebral  joints  are  involved  a  flexor  spasm  may  predomi- 

1  Jour.  Am.  Med.  Assn.,  1915,  Ixv,  p.  1989. 


THE  JOINTS  307 

nate  while  an  extensor  spasm  is  more  frequent  if  the  articulations  of 
the  laminae  are  the  seat  of  the  pathology.  One  characteristic  of  the 
condition  is  that,  as  a  rule,  only  a  limited  number  of  vertebrae,  usually 
six  to  eight,  are  affected,  although  sometimes  the  whole  dorsal  area 
or  even  the  entire  spine  is  involved.  Pain,  as  a  rule,  is  not  severe 
even  in  active  cases  and  in  the  synovial  form  the  x-ray  is  negative. 
Another  striking  characteristic  of  these  conditions  is  a  hypotonicity 
of  the  ligaments  and  muscles  of  the  uninvolved  portions  of  the 
spine,  the  sacro-iliac  joints  and  the  hips.  Thus  in  patients  with 
localized  stiffness  as  well  as  in  those  with  general  stiffness  many 
were  able  to  touch  the  floor  with  their  fingers  while  keeping  the 
knees  stiff.  While  some  were  able  to  place  their  palms  on  the  floor 
and  two  or  three  could  bend  their  elbows  while  still  keeping  their 
knees  stiff.  This  hypotonicity  with  localized  stiffness  in  the  spine 
is  considered  by  Whitney  and  Baldwin  as  almost  pathognomonic 
of  syphilis. 

Charcot's  Joint. — As  stated  above,  Charcot's  joint  is  either  an 
accompaniment  or  precursor  of  tabes  dorsalis.  There  is  usually 
the  history  of  an  injury,  as  with  a  patient  of  the  author  who  fell 
from  a  table,  his  weight  falling  on  his  right  hand  with  the  arm 
extended.  However,  the  frequency  of  this  condition  in  syringo- 
myelia leads  to  the  conclusion  that  it  is  due  to  the  spinal  lesion  with 
the  injury  as  the  exciting  cause.  The  first  symptom  is  usually  an 
.abnormal  range  of  motion.  This  is  followed  by  marked  swelling, 
with  no  redness  or  tenderness,  and  pain  is  slight  or  absent.  While 
the  large  joints  are  usually  affected,  no  joint  is  exempt.  Nearly 
complete  resolution  may  occur  or  the  condition  may  go  on  until, 
as  Church  and  Peterson^  remark,  "Old  tabetic  joints  present, 
merely  a  bag  of  bone  fragments  where  articulations  were  formerly 
located." 

Diagnosis. — The  simple  arthralgia  occurring  early  in  the  course 
of  syphilis  should  present  no  difficulty  of  diagnosis,  as  it  is  usually 
an  accompaniment  of  the  cutaneous  lesions.  If,  as  sometimes 
happens,  arthralgia  is  noted  before  he  appearance  of  any  ■  utaneous 
lesions,  and  a  chancre  is  not  found,  the  diagnosis  may  be  impos- 
sible, as  no  pathological  change  is  demonstrable,  and,  as  a  rule, 
the  laboratory  tests  are  negative. 

The  acuts  synovitis  of  syphilis  may  be  mistaken  for  acute  articular 
rheumatism  but  the  usual  absence  of  fever,  and  acid  sweats  will 
be  suspicious,  even  without  a  history  of  chancre  or  the  presence  of 
other  syphilitic  manifestations.  This  condition  may  also  be  mis- 
taken for  gonorrheal  arthritis,  but  the  history  of  gonorrheal  ure- 
thritis or  its  presence  in  chronic  form,  and  the  fact  that  the  gonor- 

1  Nervous  and  Mental  Diseases,  Philadelphia  and  London,  1911.  p.  446. 


308  SYPHILIS  OF   THE  BONES,   JOINTS,   BURS^ 

rheal  arthritis  is  more  acute  and  painful  than  the  syphihtic  condition, 
will  usually  serve  as  diagnostic  points.  The  complement-fixation 
test  for  gonorrhea  as  well  as  the  Wassermann  test  may  also  be  of 
value,  although  it  must  be  remembered  that  syphilis  and  gonorrhea 
are  not  infrequently  associated  in  the  same  individual  and  that 
either  disease  alone  or  both  may  be  the  cause  of  the  joint  affection. 

The  chronic  synovitis  of  syphilis  may  be  diagnosed  as  rheumatoid 
arthritis,  but  the  latter  condition  is  more  chronic,  there  is  more 
bony  deformity  and  there  is  grating  of  the  joint  which  is  absent 
in  syphilis. 

Gummatous  affections  of  the  joints  must  be  differentiated  from 
tuberculosis.  In  the  latter  condition  the  pain  is  greater,  the  process 
more  rapid,  while  there  is  a  general  thickening  of  the  synovial 
membrane  instead  of  the  usual  gummatous  nodules  seen  in  the 
syphilitic  disease. 

Charcot's  joint  can  usually  be  diagnosed  by  the  abnormal  range 
of  motion,  the  marked  swelling  without  redness  or  tenderness,  the 
slight  or  absent  pain  and  the  usual  presence  of  other  symptoms  of 
tabes. 

The  same  remarks  may  be  made  concerning  syphilitic  joint 
disease  in  general  as  were  made  concerning  bone  syphilis,  namely, 
that  the  history,  the  presence  or  absence  of  concomitant  syphilitic 
lesions,  the  laboratory  findings  and  the  therapeutic  tests  are  of 
more  importance  in  diagnosis  than  the  clinical  evidence  in  the 
joints  themselves. 

With  the  joints  of  the  spine  it  must  be  remembered,  as  pointed 
out  above,  that  localized  stiffness  with  hypotonicity  of  the  liga- 
ments and  muscles  of  the  uninvolved  portions  as  well  as  of  those 
of  the  sacro-iliac  joints  and  the  hip  is  considered  as  almost  pathog- 
nomonic of  s^qDhilis.  However,  the  majority  of  these  cases  will 
yield  positive  results  upon  laboratory  investigation. 

Prognosis. — A  favorable  prognosis  of  syphilitic  joint  involvement 
will  depend  upon  an  early  diagnosis.  If  the  condition  is  diagnosed 
before  adhesions  have  formed  or  destruction  has  taken  place,  the 
prognosis  for  complete  restitution  under  specific  medication  is 
good.  If,  however,  adhesions  have  formed  or  marked  destruction 
occurred,  the  prognosis  for  complete  recovery  is  bad,  although,  as 
a  rule,  the  process  may  be  arrested. 

The  prognosis  of  Charcot's  joint  is  always  bad,  although  even 
in  this  serious  condition  if  the  tabetic  process  can  be  halted,  the 
arthropathy  may  also  not  progress. 

Treatment. — No  other  treatment  than  specific  and  general  is 
indicated  in  syphilitic  joint  disease,  as  a  rule,  although  if  there 
is  much  pain,  the  joint  should  be  at  rest  and  analgesics  may  be 
necessary. 


THE   TENDONS  309 

When  there  is  much  effusion  it  may  be  desirable  to  drain  off  the 
synovial  fluid  by  opening  the  joint.  The  most  rigid  aseptic  pre- 
cautions should,  of  course,  be  observed.  The  adhesions  of  syphilis 
of  the  spinial  joints  may  be  broken  up  by  forcible  manipulations. 
The  treatment  of  Charcot's  joint  consists  of  palliative  measures. 

THE   BURS^. 

Syphilis  of  the  bursse  is  a  rare  condition,  although  it  has  been 
recognized  since  the  days  of  Hunter. 

Verneuil,^  in  1873,  described  the  condition  as  occurring  early  in 
the  course  of  the  disease  and  soon  afterward  showed  that  gummata 
are  occasionally  found  in  the  bursse.  In  1876  Keyes^  published  a 
list  of  fourteen  cases.  Churchman,^  in  1909,  reviewed  the  literature 
and  reported  a  case. 

The  bursitis  of  early  syphilis  may  or  may  not  be  associated  with 
arthritis.  There  is  considerable  swelling  and  redness  of  the  skin 
while  fluctuation  may  be  noticed.  It  is  usually  accompanied  by 
other  manifestations  of  syphilis  and  occurs  at  a  time  when  the 
Wassermann  test  is  positive.  It  is  generally  transitory  and  readily 
yields  to  specific  therapy. 

Gummata  of  the  bursse  usually  occur  from  the  second  to  the 
eighth  year  but  have  been  observed  as  late  as  twenty-eight  years 
following  the  chancre  (Keyes).  This  condition  may  be  primary 
or  it  may  occur  as  an  extension  from  the  surrounding  tissues.  The 
bursse  of  the  knee  are  the  most  frequently  involved.  There  is 
a  nodular  infiltration  and  more  or  less  fluid  is  found.  The  course 
is  slow  and  insidious  and  if  left  untreated  may  extend  to  the  sub- 
cutaneous tissues  and  skin.  Pain  is  usually  slight,  although  there 
may  be  some  tenderness. 

The  diagnosis  must  rest  upon  the  history,  the  finding  of  other 
manifestations  of  syphilis,  and  positive  laboratory  evidence.  If 
the  Wassermann  and  luetin  tests  are  negative  a  portion  of  the  tumor 
should  be  removed  for  microscopic  examination. 

Gummata  of  the  bursse  as  well  as  the  earlier  syphilitic  bursitis 
usually  yield  to  specific  medication,  and  need  no  other  treatment, 
except,  perhaps,  rest  in  bed. 

THE    TENDONS. 

Syphilitic  affections  of  the  tendons  and  their  sheaths  are  of 
infrequent  occurrence.    The  process  may  at  first  attack  the  tendon 

1  Gaz.  hebd.  de  medeciniB  et  de  chirurgie,  1873,  2  S,  x,  p.  22, 

2  Am.  Jour.  Med.  Sc,  1876,  Ixxi,  p.  349. 

3  Ibid.,  1909,  cxxxviii,  p.  371. 


310  SYPHILIS  OF   THE  BONES,   JOINTS,   BURSAS 

or  the  sheath  alone  but  soon  both  become  involved.  Serous 
inflammation  of  the  sheath  with  effusion  is  rarely  seen  during  the 
first  year  of  the  disease  and  later  a  gummatous  condition  is 
sometimes  observed.  The.  former  condition  is  always  painful 
but  readily  disappears  under  specific  treatment. 

The  usual  outcome  of  the  rare  gummatous  involvement  of  the 
tendon  is  extension  to  the  surrounding  tissues  and  ulceration. 
Gummatous  infiltration  may  lead  to  thickening  and  perhaps  even 
to  calcification. 

THE   MUSCLES. 

Myalgia  similar  to  the  arthralgia  mentioned  above,  and  in  which 
no  pathological  change  of  the  muscles  can  be  detached,  is  often 
seen  early  in  the  course  of  syphilis,  sometimes  even  when  the 
chancre  is  the  only  lesion  present.  The  pain  may  be  very  slight, 
resembling  a  soreness  of  the  muscle  or  be  so  severe  that  analgesics 
will  be  required.  The  pain  may  be  worse  at  night.  Points  of  tender- 
ness are  usually  found  in  the  affected  muscle,  and  motion  generally 
aggravates  the  pain.  No  redness  or  swelling  is  observed.  The 
muscles  of  the  thighs  and  legs  are  most  frequently  affected,  although 
the  muscles  of  the  arms  and  back  are  often  involved.  Such  condi- 
tions are  most  difficult  of  diagnosis  if  other  signs  and  symptoms  of 
syphilis  are  not  present.    They  yield  readily  to  specific  medication. 

Interstitial  myositis  is  an  exceedingly  rare  condition  and  consists 
of  infiltration  of  the  connective  tissue  and  degeneration  of  the 
muscle  fibers.  It  usually  occurs  within  two  years  after  infection, 
and  there  is  a  gradual  increase  in  the  size  of  the  muscle  without 
pain,  and  without  increase  in  the  hardness.  No  redness  nor  tender- 
ness is  observed.  Contracture  soon  develops  and  the  joint  to  which 
the  muscle  is  attached  becomes  fixed.  The  process  is  most  frequently 
found  in  the  biceps  and  gastrocnemius  but  has  been  observed  in 
the  pectoralis  major,-  trapezius  and  other  muscles.  It  is  usually 
unilateral. 

Gummata  of  the  muscles  is  not  such  a  rare  condition  and  may  be 
localized  or  diffuse.  The  anatomical  picture  does  not  differ  from 
gummata  of  other  regions.  They  generally  occur  between  the  third 
and  fifth  years  of  the  disease.  If  the  condition  is  localized,  nodular 
swelling  may  be  observed  or  if  diffuse  there  will  be  general  enlarge- 
ment. There  is  practically  no  pain  or  tenderness.  The  muscles 
may  become  adherent  to  the  surrounding  tissues,  causing  more  or 
less  loss  of  function.  Often  the  process  spreads  and  involves  the 
subcutaneous  tissues  and  skin,  forming  an  ulcer.  Calcification  or 
ossification  may  occur.  Gummata  may  be  found  in  practically 
any  muscle  of  the  body  and  one  or  more  may  be  involved.  They 
must  be  differentiated  from  other  tumors,  mainly  sarcomata.    This 


THE  MUSCLES  311 

can,  of  course,  be  accomplished  by  section  of  the  growth,  or  in  most 
cases  by  the  indirect  evidence  of  history,  etc.  Koehler's  case,  as 
reported  by  Lang,^  must  be  thought  of.  In  this  case  actinomycosis 
of  the  muscles  was  incorrectly  diagnosed  as  gummatous. 

Prognosis. — The  prognosis  of  syphihs  of  the  muscles  is  good,  espe- 
cially if  diagnosed  early. 

Treatment. — It  has  been  suggested  that  local  inunctions  of  mer- 
cury over  syphilitic  muscles  is  desirable.  This,  however,  probably 
is  of  little  or  no  value  and  the  treatment,  aside  from  the  specific 
and  general,  is  rest  in  bed  with  light  massage  of  the  affected  muscles 
and  hot  packs. 

'  Steadman:  Twentieth  Century  Praotioe  of  Medicine,  New  York,  1S99,  xviii, 
p.  211. 


CHAPTER  XVIII. 
SYPHILIS  OF  THE  NERVOUS  SYSTEM. 

History. — As  early  as  1497  Leoniceno^  in  his  treatise  on  syphilis 
pointed  out  that  the  internal  organs  were  often  involved  and  that 
paralysis  sometimes  followed.  Other  writers  who  followed  him 
expressed  similar  views.  Nevertheless,  John  Hunter^  combated  the 
theory  of  syphilis  of  the  internal  organs  and  in  this  way,  as  well  as 
by  his  theory  of  the  unity  of  syphilis  and  gonorrhea,  set  back  the 
knowledge  of  syphilis  many  decades.  However,  in  1834  Lallemond'' 
showed  conclusively  that  the  brain  and  meninges  were  sometimes 
affected  with  syphilis. 

While  numerous  contributions  concerning  syphilis  of  the  nervous 
system  followed  the  work  of  Lallemond,  it  was  left  for  Virchow*  to 
describe  accurately  the  pathological  anatomy  of  gummata  of  these 
tissues.  The  next  important  article  dealing  with  syphilis  of  the 
nervous  system  was  published  by  Heubner,^  in  1874,  and  described 
the  syphilitic  involvement  of  the  cerebral  arteries. 

Since  the  time  of  Heubner  much  has  been  added  to  the  knowledge 
of  syphilis  of  the  nervous  system  and  no  other  name  stands  out  more 
prominently  than  that  of  Fournier.'^  He  it  was,  who  first  connected 
tabes  dorsaJis  with  syphilis  and  later  he  supported  the  same  theory 
in  regard  to  paresis.  It  was  not,  however,  until  1913  that  Noguchi 
and  Moore,'^  by  the  discovery  of  the  Treponema  pallidum  in  the 
brains  of  paretics  and  the  spinal  cord  of  a  tabetic,  showed  conclu- 
sively that  these  conditions  are  truly  syphilitic,  and  the  terms 
"para-  and  metasyphilitic  are  no  longer  tenable. 

Pathology. — It  has  long  been  customary  to  divide,  both  anatomic- 
ally and  clinically,  the  syphilitic  affections  of  the  nervous  system 
into  so-called  cerebrospinal  syphilis,  including  gummata,  endarteritis 
and  meningitis,  the  parasyphilitic  diseases,  paresis,  tabes  and  tabo- 
paresis, and  the  affections  of  the  peripheral  nerves.  However,  since 
the  epoch-making  work  Noguchi  and  Moore  and  further  since  Dun- 

1  Libellus  de  epidemia  quam  Itali  morbum  gallicum  vocant  vulgo  brossulas,  Venice, 
1497. 

2  A  Treatise  on  the  Venereal  Diseases,  Philadelphia,  1859,  p.  410. 

^  Recherches  anatomo-pathologique  sur  I'Encephale,  Paris,  1834,  t,  iii. 

4  Virchows  Arch.  f.  path.  Anat.,  1858,  xv,  p.  229. 

5  Die  luetische  Erkrankung  der  Hirnarterien,  etc.,  Leipsig,  1874. 

6  De  I'Ataxie  locomotrice  d'origine  syphilitique,  Paris,  1876. 

7  Jour.  Exper.  Med.,  1913,  xvii,  p.  232. 


PATHOLOGY  313 

lap^  has  pointed  out  that  certain  cases  exist  that  may  be  termed 
border-line  cases  which  anatomically  may  be  interpreted  as  belong- 
ing to  either  group,  it  seems  best  to  consider  the  pathology  of  the 
central  nervous  system  under  the  following  headings : 

1.  Meninges. 

2.  Arteries. 

3.  Brain  Substance. 

4.  Cord  Substance. 

5.  Nerves. 

It  must  be  understood,  however,  that  the  majority  of  the  cases 
will  show  more  than  one  pathological  condition,  for  example,  it  is 
hard  to  conceive  of  a  basic  meningitis  in  which  the  circle  of  Willis  is 
not  more  or  less  affected  by  an  arteritis. 

Meninges. — That  the  meninges  may  be  the  seat  of  syphilitic 
involvement  early  in  the  course  of  the  disease  has  been  deduced 
both  by  clinical  evidence  and  by  lumbar  puncture.  No  one,  how- 
ever, as  far  as  the  author  is  aware,  has  described  the  pathological 
anatomy  in  early  syphilitic  involvement  of  the  meninges.  Later 
in  the  course  of  the  disease  meningitis  may  occur  as  a  diffuse  inflam- 
matory process,  or  as  a  gummatous  condition.  It  may  involve  all 
three  of  the  enveloping  coats  of  the  brain  and  spinal  cord.  It  may 
originate  in  the  bones  or  periosteum  and  later  affect  the  meninges 
or  the  meninges  may  primarily  be  involved. 

The  diffuse  inflammatory  meningitis  is  characterized  by  an  exuda- 
tion of  endothelial  cells  and  polymorphonuclear  leukocytes  and  the 
formation  of  fibrin.  There  is  generally  a  marked  infiltration  of 
lymphocytes,  and  giant  cells  are  usually  observed,  while  trepone- 
mata  are  more  or  less  abundant.  It  is  probable  that  this  is  the  type 
of  meningitis  which  exists  when  the  meninges  are  involved  early  in 
the  course  of  the  disease. 

Gummatous  meningitis,  which  usuall}^  complicates  the  inflamma- 
tory type  may  be  either  a  diffuse  process  or  consist  of  circumscribed 
nodules  of  varying  size.  Any  one  of  the  membranes  may  be  affected 
alone,  but  it  is  usual  for  all  to  be  involved.  The  gummatous  menin- 
gitis usually  is  associated  with  a  fibrous  hyperplastic  condition  in 
which  the  dura  may  be  several  times  thicker  than  normal.  The 
leptomeninges  usually  are  adherent,  thickened  and  contain  gum- 
matous deposits  either  diffuse  or  circumscribed. 

Circumscribed  gummata  of  the  meninges  vary  in  size  from  one 
millimeter  to  several  centimeters  and  may  be  found  in  any  location. 
They  usually  appear  in  the  fresh  state  as  grayish-red  nodules  but 
may  be  of  a  yellowish  tint. 

The  most  frequent  seat  of  both  the  circumscribed  and  diffuse  type 

1  Am.  Jour.  Insan.,  1913,  Ixix,  p.  1045. 


314  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

of  gummatous  meningitis  is  the  base  of  the  brain  and  from  here  it 
may  involve  the  cranial  nerves,  extend  down  the  meninges  of  the 
cord  and  affect  the  spinal  nerves.  On  the  base,  the  region  of  the 
chiasm  and  interpeduncular  space  are  most  often  affected.  The 
convexity  of  the  brain  is  also  usually  involved  and  rarely  may  be 
the  sole  seat  of  the  pathology. 

The  meninges  of  the  cord  alone  may  be  invaded  by  the  syphilitic 
process.  The  most  frequent  location  seems  to  be  the  cervical  region, 
while  it  is  most  often  observed  on  the  posterior  surface  of  the  cord. 
However,  the  condition  may  completely  surround  the  cord  like  a 
collar.    The  lumbar  region  is  very  rarely  affected  alone. 

Arteries. — Arteritis  probably  is  the  most  constant  syphilitic 
manifestation  in  the  central  nervous  system,  as  the  arteries  are 
almost  always  found  more  or  less  involved  with  all  other  types  of 
pathological  lesion.  In  fact  the  arteries  may  be  the  starting-point 
of  other  types  of  syphilis  of  the  nervous  system.  The  arteries  of  the 
base  of  the  brain  are  the  most  frequently  involved.  They  are  thick- 
ened and  tough,  due  to  the  infiltration  of  the  adventitia  and  the 
hyperplasia  of  the  endothelial  cells  of  the  intima.  This  hyperplasia 
may  be  so  extensive  as  to  produce  complete  obliteration.  This 
obliteration  of  the  vessels  may  lead  to  encephalomalacia.  Rupture 
of  the  cerebral  arteries  with  or  without  aneurysm,  followed  by  sec- 
ondary hemorrhage  is  of  frequent  occurrence.  Arteritis  of  the 
vessels  of  the  spinal  cord  with  obliteration  will  lead  to  myelitis. 
Treponemata  have  occasionally  been  demonstrated  in  the  arteries 
of  the  brain. 

Aside  from  the  specific  process  in  the  arteries  themselves  they  may 
become  diseased,  due  to  compression  of  gummata  in  the  perivascular 
tissues.  The  veins  of  the  central  nervous  system,  as  well  as  those  of 
other  localities,  may  also  be  the  seat  of  syphilitic  inflammation. 

Brain  Substance. — Syphilis  of  the  brain  substance  occurs  in  two 
types  (jummatous  formation  and  diffuse  infiltration  of  the  gray  matter 
with  treponemata. 

Gummata  of  the  brain  usually  occur  in  the  gray  matter,  but  may 
be  found  in  any  locality,  and  while  they  generally  originate  in  the 
meninges  and  spread  to  the  cortex  they  may  begin  in  the  brain  sub- 
stance itself.  They  are  usually  multiple,  of  irregular  outline,  and, 
if  situated  near  the  surface,  are  generally  associated  with  a  diffuse 
meningitis. 

Upon  section  a  gumma  in  the  fresh  state  presents  a  yellowish, 
dense  mass  in  the  centre,  which  is  surrounded  by  a  grayish  zone 
which  varies  in  consistency  and  which  in  turn  is  surrounded  by  a 
reddish  area.  Microscopically,  the  central  portion  is  seen  to  be  a 
necrotic  mass,  which  may  contain  giant  cells,  the  other  cells  being 
indistinguishable,  while  the  periphery  is  composed  of  granulation 


PATHOLOGY 


315 


and  fibrous  tissue.  Trepoiiemata  rarely  have  been  demonstrated  in 
cerebral  gummata.  Uhle  and  Mackinney^  have  reported  the  finding 
of  the  organisms  in  such  lesions. 

Diffuse  infiltration  of  the  gray  matter  of  the  brain,  especially  the 
cerebrum,  with  treponemata  results  in  little  immediate  injury. 
However,  a  proliferation  of  the  glia  cells  slowly  occurs  with  atrophy 
and  disappearance  of  the  ganglion  cells  and  more  or  less  resulting 
sclerosis.  Tl)is  is  the  pathological  picture  observed  in  paresis,  to 
which  are  added  other  abnormal  findings  such  as  meningitis,  endar- 
teritis, etc.    The  treponemata  are  found  in  groups  or  singly  among 


Fig.  67. — Base  of  paretic  brain. 

the  nerve  cells  and  neuroglia  fibers.  They  may  sometimes  be 
observed  to  have  become  partially  inserted  in  the  nerve  cell. 

Cord  Substance. — The  pathological  findings  in  syphilis  of  the 
substance  of  the  spinal  cord  are  similar  to  those  found  in  the  brain. 

Gummata  of  the  cord  may  occur  in  any  locality  and  usually  origi- 
nate in  the  meninges  but  very  rarely  arise  in  the  substance  of  the 
cord.  The  macroscopic  and  microscopic  pictures  differ  in  no 
way  from  gummata  of  the  brain.  Myelitis  due  to  occlusion  of  the 
bloodvessels  of  the  cord  usually  is  found  in  the  gray  substance.    In 


1  Proc.  Path.  Soc,  PhUadelphia  (N.  S.),  1906,  ix,  p.  195. 


316 


SYPHILIS  OF  THE  NERVOUS  SYSTEM 


rare  instances  the  lesion  may  involve  the  entire  cross-section.  It  is 
almost  always  associated  with  meningitis,  and  is  followed  by  ascend- 
ing and  descending  degenerations.  Both  grossly  and  microscopically 
syphilitic  myelitis  differs  but  little  from  that  due  to  other  causes. 


Fig. 


-Treponema  pallidum  in  the  brain  of  a  paretic.     (Moore.) 


There  is  congestion  of  the  bloodvessels  with  rupture  of  some  of  them 
and  hemorrhage  into  the  gray  matter.  The  ganglion  cells  are  dis- 
torted with  broken  processes  and  are  more  or  less  destroyed,  some  of 
them  completely  so. 


CLINICAL  HISTORY  317 

Diffuse  infiltration  of  the  spinal  cord,  especially  the  posterior 
columns  with  treponemata,  produces  changes  similar  to  those 
obser\'ed  in  the  brain,  and  these  changes,  plus  other  pathological 
conditions,  as  meningitis,  constitute  the  anatomical  picture  of  tahes 
dorsal  is. 

Noguchi^  has  been  able  to  demonstrate  the  Treponema  pallidum 
in  the  posterior  column  of  the  dorsal  portion  of  the  spinal  cord  in 
tabes. 

When  there  is  an  infiltration  of  the  treponemata  into  the  gray 
matter  of  the  brain  as  well  as  into  the  cord  with  the  resultant 
changes,  the  condition  is  described  as  taboparesis. 

Nerves. — The  nerves  may  be  affected  by  syphilis  either  directly 
or  indirectly.  When  directly  affected  the  process  is  usually  an 
extension  from  the  meninges  to  the  nerve  roots.  The  interstitial 
substance  is  infiltrated  with  granulation  tissue  which  slowly  is 
changed  into  more  or  less  dense  fibrous  tissue.  Endarteritis  of  the 
nutrient  vessels  causing  interference  with  the  circulation  is  often 
observed.  Marked  degeneration  follows  these  changes.  A  Gum- 
matous process  of  the  nerves  occasionally  is  observed  and  presents 
either  a  diffuse  thickening  or  circumscribed  nodules,  like  beads  on  a 
string.  Indirectly  the  nerves  may  be  affected  by  pressure  either  of 
a  gumma  or  by  periosteal  thickening  as  they  pass  through  a  bony 
canal. 

Clinical  History. — It  has  been  pointed  out  above  that  while  certain 
changes  in  one  tissue  of  the  nervous  system,  such  as  the  meninges, 
may  dominate  the  pathological  picture,  the  process  is  usually  not 
limited  to  one  tissue  but  that  others  are  more  or  less  involved. 
Therefore,  as  would  be  expected,  the  clinical  signs  and  symptoms 
are,  as  a  rule,  not  limited  to  those  produced  by  involvement  of 
one  tissue,  although  such  symptoms  may  be  most  prominent. 

Meninges. — That  the  meninges  may  be  involved  in  the  syphilitic 
process  early  in  the  course  of  the  disease  was  pointed  out  above. 
The  earliest  date  following  infection  at  which  involvement  of  the 
central  nervous  system  has  been  noted  in  the  case  reported  by  Read,- 
in  which  marked  symptoms  were  present  two  weeks  after  the  appear- 
ance of  the  chancre.  Several  other  investigators  have  reported  cases 
of  syphilis  in  which  the  chancre  was  present,  but  no  cutaneous 
manifestations  had  appeared  in  which  either  clinical  symptoms  or 
spinal  puncture  or  both  revealed  involvement  of  the  central  nervous 
system. 

Wechselmann^  found  positive  evidence  of  involvement  of  the 
central  nervous  system  in  the  spinal  fluid  of  6  such  cases,  while  in 
only  3  were  there  any  clinical  symptoms  present. 

1  Jour.  Cut.  Dis.,  1913.  xxxi,  p.  543.  ^  XJrologic  and  Cut.  Rev.,  1915,  xix,  p.  75. 

2  Deutsch.  med.  Wchnschr.,  1912,  xxxviii,  p.  1446. 


318  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

FrankeP  reported  2  cases  in  both  of  which  the  spinal  fluid  was 
negative  and  clinical  symptoms  of  central  nervous  involvement  were 
absent. 

Altmann  and  Dryfus^  found  the  spinal  fluids  of  2  out  of  8  cases 
positive. 

Leopold*  examined  16  cases  in  which  the  chancre  was  the  only 
evidence  of  syphilis.  In  6  there  were  clinical  signs  as  well  as  posi- 
tive findings  in  the  spinal  fluid,  showing  that  the  central  nervous 
system  was  affected. 

Wile  and  Stokes*  reported  6  cases  which  were  observed  during  the 
so-called  second  incubation  period,  that  is,  before  any  skin  mani- 
festations had  appeared.  Neurological  examinations  as  well  as 
examinations  of  the  fundus  oculi  and  the  eighth  nerve  were  made  on 
all  cases.  Lumbar  puncture  was  made  on  all  but  1.  These  investi- 
gators found  both  clinical  and  spinal  fluid  evidence  of  involvement 
of  the  central  nervous  system  in  4  of  the  cases.  One  case  showed 
slight  clinical  evidence  with  a  normal  spinal  fluid,  while  1  case, 
the  only  one  which  had  had  treatment,  showed  only  a  beginning 
arteriosclerosis  and  slight  involvement  of  the  eighth  nerve,  lumbar 
puncture  having  been  unsuccessful. 

The  author  has  examined  for  evidence  of  involvement  of  the 
central  nervous  system  but  5  cases  of  cliancre  in  which  no  cutaneous 
manifestation  was  present.  Of  these  5  only  1  would  consent  to 
lumbar  puncture. 

The  following  is  a  summary  of  the  cases : 

Case  1. — A.  S.,  male,  aged  twenty-six  years;  laborer.  Family 
and  past  history  negative.  Small  papular  chancre  of  glans  developed 
three  weeks  after  exposure.  Was  seen  two  weeks  after  appearance 
of  lesion.  Had  had  no  treatment  but  "salve."  Adenopathy  local 
only.  Many  treponemata  demonstrated  by  dark-field  illumination. 
Lower  tendon  reflexes  slightly  exaggerated.  Ankle-clonus,  Babinski 
and  Romberg  negative.  Pupils  regular  in  outline,  equal  in  size  and 
react  normally  to  light  and  accommodation.  Slight  retinitis  in  both 
eyes.  Spinal  fluid  showed  no  apparent  increase' in  pressure;  three 
lymphocytes  per  cubic  millimeter,  negative  globulin  (author's  modi- 
fication of  Noguchi's  butyric  acid  test),  negative  Wassermann; 
negative  Lange  colloidal  gold  test ;  Wassermann  dn  blood  -| — | — 1- . 

Case  2. — L.  R.,  male,  aged  twenty-three  years;  cowboy.  Family 
and  past  history  negative.  Unable  to  determine  incubation  period, 
as  had  been  exposed  numerous  times  during  the  month  previous  to 
appearance  of  large  indurated  chancre  of  balanopreputial  fold.    Was 

1  Ztschr.  f.  ges.  Neurol,  u.  Psychiat.,  1912,  ix,  p.  1. 

2  Munchen.  med.  Wchnschr.,  1913,  Ix,  pp.  464,  530. 

3  Dermat.  u.  Syph.,  1914,  cxx,  p.  101. 

4  Jour.  Am.  Med.  Assn.,  1915,  Ixiv,  p.  979. 


CLINICAL  HISTORY  319 

seen  one  week  after  appearance  of  lesion.  Adenopathy  sliglit  and 
local  only.  Many  treponemata  demonstrated  by  dark-field  illumi- 
nation. All  neurological  tests  negative,  as  well  as  a  normal  fundus 
oculi  observed.  Lumbar  puncture  refused.  Wassermann  on  blood 
negative. 

Case  3. — H.  R.,  male,  aged  thirty-two  years;  carpenter.  Family 
and  past  history  negative.  Chancre  of  lower  lip  appeared  two  weeks 
after  exposure.  Was  seen  three  weeks  after  appearance  of  lesion. 
Enlargement  of  submaxillary  glands.  Few  treponemata  demon- 
strated by  dark-field  illumination.  Lower  tendon  reflexes  slightly 
exaggerated.  Ankle-clonus  and  Babinski  negative.  Slight  positive 
Romberg.  Pupils  equal  in  size,  regular  in  outline  but  react  some- 
what sluggishly  to  Hght  and  accommodation.  Retinitis  in  both 
eyes.    Lumbar  puncture  refused.    Wassermann  on  blood  -\ — | — |-. 

Case  4. — J.  C,  male,  aged  nineteen  years;  dishwasher.  Family 
and  past  history  negative.  Papule  developed  on  balanopreputial 
fold  sixteen  days  after  exposure.  Was  seen  five  weeks  after  appear- 
ance of  lesion.  Ulcerating  chancre  on  balanopreputial  fold  with 
marked  inguinal  adenopathy.  Treponemata  could  not  be  demon- 
strated by  dark-field  illumination.  Neurological  examination  nega- 
tive, except  for  slight  exaggerated  lower  tendon  refiexes  and  posi- 
tive Romberg.  Fundus  oculi  normal.  Lumbar  puncture  refused. 
Wassermann  on  blood  -\ — | — | — h  • 

Case  5. — J.  A.,  male,  aged  nineteen  years;  student.  Family  and 
past  history  negative.  Eleven  days  after  intercourse  noticed  slight 
burning  of  urethra  on  urination,  which  was  followed  the  next  day 
by  a  slight  "whitish"  discharge.  A  physiciapi  was  consulted  who 
irrigated  the  urethra  with  potassium  permanganate  solution  and 
gave  him  another  solution  for  self-injection.  There  was  no  improve- 
ment; in  fact,  the  condition  grew  worse.  He  consulted  the  author 
three  weeks  later  and  an  examination  revealed  the  following :  There 
was  a  marked  edema  of  the  prepuce  with  phimosis  and  a  copious 
purulent  discharge.  Gonococci  could  not  be  demonstrated.  An 
indurated  area  about  1  cm.  in  diameter  could  be  plainly  felt  on  the 
under  surface  of  the  penis  near  the  frenum.  The  inguinal  glands  on 
both  sides  were  markedly  enlarged.  No  other  glandular  enlarge- 
ment could  be  detected.  The  neurological  examination  revealed  the 
lower  tendon  reflexes  markedly  exaggerated,  the  knee-jerks  being 
explosive  in  character.  Upper  tendon  reflexes  slightly  exaggerated. 
Ankle-clonus  negative.  Romberg  negative.  Pupillary  reflexes 
normal.  Ophthalmoscopic  examination  of  the  right  eye  showed  the 
retina  normal  except  at  the  border  of  the  disk  corresponding  to  the 
lower  nasal  side,  where  a  distinct  swelling  was  noted.  The  vessels 
were  seen  to  dip  and  a  part  were  completely  hidden  as  they  passed 
onto  the  disk.     The  border  of  the  disk  was  obliterated  to  the  extent 


320  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

of  the  swelling,  that  is,  about  one-fifth.  The  left  eye  showed  a 
normal  retina.  At  the  lower  margin  of  the  disk  there  was  a  cloudi- 
ness which  hid  the  border.    There  was  no  swelling  present. 

Lumbar   puncture   was    refused.      Wassermann    on   the    blood 

+  +  +  +•.. 
Numerous  investigators  have  reported  the  involvement  of  the 

nervous  system  slightly  later  in  the  course  of  the  disease,  that  is, 

during  the  early  active  cutaneous  manifestations.    Wile  and  Stokes^ 

go  so  far  as  to  state  "that  in  all  probability  every  case  of  syphilis 

which  reaches  the  secondary  period  has  more  or  less  involvement  of 

the  cerebrospinal  axis." 

Ravaut^  reported  67  per  cent,  involved.  Ellis^  reported  6  cases 
of  early  syphilitic  meningitis.  Swift  and  Ellis^  found  36  per  cent, 
affected.  Wile  and  Stokes^  reported  the  apparent  involvement 
of  66.7  per  cent,  of  a  series  of  36  cases,  while  Fordyce^  found  less 
than  20  per  cent,  with  involvement  of  the  central  nervous  system. 

Of  31  cases  of  early  active  cutaneous  lesions,  that  is,  during  the 
first  year  of  the  disease,  which  have  come  under  the  observation  of 
the  author,  and  have  been  examined  neurologically,  9,  or  30  per 
cent.,  have  shown  some  positive  evidence  of  involvement  of  the 
central  nervous  system.  No  spinal  fluid  examinations  were  made, 
and  such  symptoms  as  headache,  while  probably  due  to  involvement 
of  the  meninges,  were  not  considered  positive  evidence. 

Syphilitic  meningitis  may  also  occur  late  in  the  course  of  the 
disease;  in  fact,  Ricord  classified  syphilis  of  the  nervous  system 
with  his  so-called  tertiary  manifestations. 

The  symptoms  of  syphilitic  meningitis  of  the  brain  will  depend 
upon  the  location  of  the  involvement,  although  it  cannot  always 
be  determined  from  the  symptoms  whether  the  convexity  or  base 
is  involved  or  whether  both  locations  are  the  seat  of  the  pathological 
process. 

Base. — Headache  is  the  most  frequent  symptom  of  specific  menin- 
gitis of  the  base  of  the  brain.  It  is  present  in  practically  all  cases 
and  may  be  the  only  s}Tnptom  observed  for  a  very  long  time.  It 
is  usually  paroxysmal  in  character  and  is  described  as  boring,  split- 
ting, stabbing,  throbbing.  Between  the  severe  paroxysms  there  may 
be  a  dull  ache.  Not  infrequently  there  may  be  severe  pain  deep  in 
the  orbits  of  the  eyes  and  sometimes  the  headache  is  localized  upon 
the  forehead  or  over  the  eyes.  Vertigo  and  even  reeling  and  stagger- 
ing are  often  noted. 

1  Jour.  Am.  Med.  Assn.,  1915,  Ixiv,  p.  979.  2  Presse  med.,  1912,  xx,  p.  181. 

3  Jour.  Am.  Med.  Assn.,  1912,  lix,  p.  1263. 

*  Forschheimer :  Therapeutics  of  Internal  Diseases,  New  York  and  London,  1914, 
V,  p.  401. 

5  Jour.  Cut.  Dis.,  1914,  xxxii,  p.  607. 

6  Am.  Jour.  Med.  Sc,  1915,  cxlix,  p.  781. 


CLINICAL  HISTORY  321 

Vomiting,  which  often  occurs  without  food  in  the  stomach,  is  a 
very  frequent  symptom,  although  not  a  constant  one,  and  may 
precede  all  other  symptoms.  The  temperature  is  usually  normal, 
but  may  be  slightly  elevated.  A  very  high  temperature  may  be 
considered  a  complication.  Polydipsia  and  polyuria  are  rpther 
common  symptoms,  while  diabetes  mellitus  has  been  observed. 

The  psychic  symptoms  vary  greatly.  The  most  frequent  condi- 
tion is  one  of  stupor  from  which  the  patient  may  be  aroused  tem- 
porarily. There  may  be  a  purposeless  motor  delirium.  More  or 
less  complex  acts  may  be  performed  on  command,  although  the 
urine  and  feces  may  be  passed  in  bed.  There  is  usually  loss  of 
memory,  especially  for  recent  events,  and  a  disorientation  for  time 
and  place.  There  may  be  more  or  less  periods  of  excitement  or 
there  may  be  marked  depression  with  suicidal  tendency.  Conscious- 
ness may  last  for  a  long  time,  followed  by  the  sudden  appearance 
of  coma  and  death. 

General  convulsions  of  an  epileptiform  type  are  often  observed 
or  there  may  be  partial  or  unilateral  convulsions. 

The  cranial  nerves  are  usually  more  or  less  affected.  The  result- 
ing conditions  will  be  described  under  Syphilis  of  the  Nerves. 

Convexity. — When  the  meninges  of  the  convexity  of  the  brain 
are  involved,  as  with  the  base,  the  most  constant  symptom  is  head- 
ache. However,  in  this  condition,  while  the  headache  may  be  severe 
and  diffuse,  although  it  may  be  dull,  there  is  usually  also  a  definite 
severe  pain  localized  in  some  particular  spot.  Most  authors  state 
that  this  is  worse  at  night,  although  this  is  not  always  the  case. 
There  is  usually  localized  tenderness  on  pressure  and  percussion 
and  a  difference  in  the  percussion  note  may  be  observed. 

The  psychic  state  is  usually  one  of  progressive  dementia.  There 
is  loss  of  memory  with  apathy;  delirium,  however,  may  exist. 

Neurological  symptoms  will  depend  upon  the  exact  location  and 
severity  of  the  process.  There  may  be  cortical  convulsions  which 
may  be  general  and  indistinguishable  from  idiopathic  epilepsy  or 
they  may  be  confined  to  one  extremity  or  even  to  a  part  of  one, 
such  as  the  finger. 

Gummata  of  the  meninges  will  cause  symptoms  depending  upon 
their  size  and  location.  There  will  be  more  or  less  increase  of  intra- 
cranial pressure  with  symptoms  of  tumor,  vomiting,  choked  disk, 
vertigo,  slow  pulse  and  stupor.  There  may  also  be  focal  symptoms 
pointing  to  the  location  of  the  lesion  or  lesions  such  as  monoplegia, 
hemiplegia  or  Jacksonian  epilepsy. 

Meningitis  of  the  Cord. — The  meninges  of  the  cord  alone  may  be 
involved  in  the  syphilitic  process,  although  it  is  more  usual  for  men- 
ingitis of  the  brain  to  coexist.    The  symptoms  of  specific  meningitis 
of  the  cord  consist  of  stiffness  and  pains  in  the  neck,  back  and 
21 


322  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

sacrum.  These  pains  may  be  severe  but  are  not  always  so.  Pains 
radiating  in  the  arms  and  legs  and  trunk  are  often  noted.  There 
may  be  numbness  and  tingling  sensations,  areas  of  paresthesia 
and  hyperesthesia  are  often  found.  The  so-called  girdle  pain  is 
very  frequent.  The  back  is  usually  more  or  less  rigid  and  there 
are  spots  along  the  spine  which  are  tender  to  percussion.  Kernig's 
sign  is  often  present.  The  superficial  and  deep  reflexes  are  exagger- 
ated. If  the  meningeal  exudate  be  extensive,  symptoms  of  compres- 
sion myelitis  will  develop. 

Arteries. — It  has  been  pointed  out  above  that  syphilitic  arteritis 
and  meningitis  usually  occur  together,  although  the  clinical  and 
pathological  picture  may  be  dominated  by  the  more  extensive 
involvement  of  one  or  the  other.  Syphilitic  arteritis  occurs  as 
early  as  the  third  or  fourth  month  after  infection,  but  is  usually 
a  later  manifestation,  being  observed  from  the  third  to  the  tenth 
year  and  often  very  much  later. 

The  symptoms  of  syphilitic  arteritis  of  the  central  nervous  sys- 
tem will  naturally  depend  upon  the  location  of  the  arteries  affected 
and  the  extent  of  the  process.  When  the  brain  arteries  are  involved 
monoplegia  and  hemiplegia  are  very  frequent  and  the  first  sjinptom 
may  be  an  apoplectic  attack,  although  there  may  be  such  prodromal 
symptoms  as  headache,  which  is  usually  not  so  severe  as  in  menin- 
gitis, dizziness,  insomnia,  loss  or  impairment  of  memory,  lack  of 
ambition,  irritability,  inability  to  concentrate  on  mental  effort, 
etc.  All  these  symptoms  are  explainable  by  the  pathology,  although 
they  may  occur  in  other  conditions.  There  may  be  transient  motor 
disturbances  such  as  slight  clonic  contractions  of  the  extremities 
or  there  may  be  transient  paralyses. 

The  onset  of  a  hemiplegia  may  be  quite  sudden  with  varying 
symptoms  of  apoplexy  such  as  giddiness,  nausea,  stupor  and  even 
complete  loss  of  consciousness.  Sometimes  there  are  convulsions. 
If  the  attack  is  slight,  it  is  usually  transitory  in  character.  Often 
the  condition  is  that  of  a  monoplegia,  the  symptoms  depending 
upon  the  location  of  the  trouble.  Not  infrequently  there  may  be 
an  aphasia,  usually  motor  in  character,  either  appearing  as  the 
only  symptom  or  in  combination  with  a  monoplegia  or  a  hemi- 
plegia. 

Marked  involvement  of  the  basilar  artery  will  cause  symptoms 
of  pons  affection,  and  is  usually  fatal. 

Disturbances  of  sensation  are  rare.  Quite  often  the  pupils  show 
anomolies,  being  irregular  in  outline  of  different  size  and  reacting 
sluggishly  or  not  at  all  to  light. 

Homonymous  hemianopsia  due  to  involvement  of  the  posterior 
cerebral  artery,  thus  affecting  the  optic  radiations  and  calcarine 
region  of  the  occipital  lobe,  is  occasionally  found. 


•      CLINICAL  HISTORY  323 

Affections  of  the  arteries  of  the  spinal  cord  will  cause  more  or 
less  myelitis,  the  symptoms  of  which  will  be  described  later. 

Brain  Substance. — Gummata  of  the  brain  substance  are  rather 
rare  and  will  produce  symptoms  of  brain  tumor  depending  upon  the 
location,  number  and  size. 

Paresis. — The  clinical  picture  called  paresis  or  dementia  para- 
lytica is  now  known  to  be  a  syphilitic  condition  due  to  the  diffuse 
infiltration  of  the  gray  matter  of  the  brain  with  treponemata, 
with  the  resulting  changes,  and  the  old  saying  "no  syphilis  no 
paresis"  is  proven  to  be  true.  And  while  there  are  certain  cases 
which  both  anatomically  and  clinically  may  be  difficult  or  impos- 
sible of  classification,  as  a  rule  the  picture  in  paresis  is  of  sufficient 
clearness  to  make  it  unmistakable. 

The  date  of  onset  of  paresis  in  respect  to  the  syphilitic  infection 
is  in  a  large  percentage  of  cases  difficult  to  determine,  but  it  is  usually 
a  late  occurrence,  developing,  as  a  rule,  from  ten  to  fifteen  years 
after  the  chancre.  The  earliest  development  of  paresis  which  the 
author  has  seen  was  five  years  after  contracting  syphilis.  Kraep- 
elin^  cites  a  case  occurring  three  years  after  infection  and  states  that 
Oliver  reported  a  case  developing  forty-four  years  following  infection. 

The  symptoms  of  paresis  are  varied  and  complex  and  may  be 
divided  into  mental,  neurological  and  general. 

Mental  Symptoms. — The  psychic  phenomena  of  paresis  may  be 
said  to  be  represented  by  a  peculiar  mental  failing,  at  times  asso- 
ciated with  a  delusional  trend,  changes  in  mood,  and  periods  of 
excitement  and  depression. 

One  of  the  earliest  evidences  of  on-coming  paresis  is  a  change  in 
moral  tone.  Not  only  may  the  model  husband  and  father,  the  "  pillar 
of  the  church"  fall  from  his  high  moral  plane,  be  heard  to  utter 
oaths,  seek  lewd  companions  and  revel  in  licentiousness,  but  on 
the  other  hand,  the  roue  often  becomes  highly  moral,  seeks  religion, 
or,  as  in  a  case  of  the  author's,  actually  becomes  a  minister  and  seeks 
to  save  sinners. 

There  is  usually  an  early  absent-mindedness,  an  inattention,  and 
failure  to  grasp  details  of  every-day  life.  Often  in  a  general  conver- 
sation there  is  a  failure  to  hear  questions  asked  and  sometimes 
answers  are  given  to  questions  directed  to  others. 

The  ability  to  concentrate  is  lost  early  in  the  disease,  the  will- 
power is  weakened,  and  there  is  a  lack  of  decision,  the  patient  may 
be  irresolute  or  he  may  be  unusually  headstrong.  He  often  makes 
serious  business  blunders.  Initiative  is  lost  and  he  can  easily  be 
influenced,  readily  falling  a  prey  to  the  business  shark.  Often 
great  business  enterprises  are  planned  which  may  even  be  started. 

1  General  Paresis,  New  York,  1913,  p.  169. 


324  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

Ability  to  understand  subtle  or  witty  conversation  is  early  lost, 
and  remarks  concerning  the  paretic  can  often  be  made  in  his  pres- 
ence without  his  comprehension.  One  of  the  early  symptoms  is 
often  a  tendency  to  tire  easily,  both  physically  and  mentally.  The 
paretic  soon  begins  to  be  careless  of  his  personal  appearance,  often 
going  unshaven  for  days. 

There  is  scarcely  ever  any  insight  into  his  condition.  Early  in 
the  course  of  the  disease  there  may  be  an  understanding  of  the 
seriousness  of  the  disorder  and  the  probable  fate.  Occasionally 
such  understanding  will  drive  the  individual  to  suicide. 

A  change  of  disposition  is  an  early  symptom.  An  excitability 
develops,  he  becomes  easily  angered  and  often  completely  loses  his 
temper,  flying  into  a  rage  at  the  slightest  provocation.  He  loses 
all  pleasure  in  mental  activities,  has  no  fear  of  danger,  and  over- 
whelming misfortune  does  not  appall  him. 

Sooner  or  later  a  grandiose  condition  develops.  He  forces  him- 
self into  prominence  and  in  conversations  becomes  boastful.  Delu- 
sions of  grandeur  are  expressed,  he  is  endowed  with  great  power,  is 
president,  a  king,  or  even  God,  himself.  These  delusions  are  usually 
not  fixed  and  can  be  changed  by  suggestion.  Later  the  excitability 
disappears  and  his  mood  corresponds  to  his  delusions,  being  happy 
with  his  delusions  of  grandeur  and  depressed  with  those  of  a  sor- 
rowful nature. 

Rapid  changes  of  mood  from  hilarity  to  tears  and  back  again  are 
brought  about  by  the  most  trival  causes,  and  are  very  character- 
istic. Sense  illusions  and  hallucinations  are  rare.  A  gradual  loss 
of  acquired  knowledge  is  seen  and  is  characterized  by  the  longest 
retentions  of  those  thought  associations  with  which  he  is  most 
familiar.  Thus,  the  mathematician  will  retain  a  knowledge  of 
arithmetic  longer  than  the  laborer. 

The  entire  catalogue  of  proprieties  may  be  outraged,  the  patient 
attending  to  the  calls  of  nature  regardless  of  his  surroundings.  He 
often  will  indulge  in  masturbation  in  the  presence  of  others. 

Loss  of  memory  occurs  early  in  the  course  of  the  disease,  and  a 
disorientation  for  time  is  observed.  He  cannot  tell  the  season  of 
the  year,  even  though  snow  be  on  the  ground  or  leaves  be  on  the 
trees.  He  may  be  able  to  give  the  date  of  his  birth  but  fail  to  tell 
his  age.  Evasive  answers  are  frequently  given  to  questions.  Lapses 
of  memory  are  often  filled  in  by  imagination.  He  draws  upon  his 
dreams  and  stories  he  has  read  to  fill  in  the  space  of  his  delusions. 

Following  a  paretic  convulsion  he  may  have  lost  all  memory  of 
recent  happenings,  not  recalling  even  his  attendants.  Occasionally 
upon  sufficient  questioning  the  paretic  can  recall  past  events  fairly 
well.  Inability  to  do  so  may  be  due  partially  to  lack  of  compre- 
hension and  upon  suggestion  may  be  overcome. 


CLINICAL  HISTORY 


325 


There  is  more  or  less  clouding  of  consciousness  which  develops 
gradually,  and  the  paretic  seems  to  live  in  a  dream  state.  Toward 
the  last  consciousness  is  entirely  lost  and  nothing  passes  beyond  the 
threshold.  Catalepsy  of  a  transitory  character  is  frequent,  also 
echolalia,  echopraxia  and  verbigeration  are  noted.  Often  there  is  a 
marked  resistiveness  such  as  mutism,  refusal  of  food  and  retention 
of  urine  and  feces. 

Toward  the  end  there  is  a  complete  suspension  of  mental  processes, 
the  patient  becomes  nothing  but  a  body  which  breathes,  passes  urine 
and  feces  involuntarily,  and  in  which  the  heart  beats,  and  to  which 
death  is  a  blessed  relief. 


Fig.  69. — Group  of  typical  paretics;     (Note  varying  expressions.) 


Neurological  Symytomsi — Of  all  the  sym.ptoms  of  paresis  the 
so-called  neurological  ones  are  the  most  character'stic,  and  are  of 
most  importance.  A  severe  headache  which  may  be  the  only  symp- 
tom present  for  a  long  time  is  of  very  frequent  occurrence.  It  is 
generally  of  a  dull,  heavy  character,  as  if  an  iron  band  were  com- 
pressing the  brain.  The  frontal  region  is  usually  most  severely 
affected. 

The  countenance  of  a  paretic  is  generally  more  of  less  changed; 
it  lacks  expression,  is  flabby  with  a  flatness  of  the  nasolabial  folds, 
which,  however,  may  be  unilateral  only,  while  silly,  almost  idiotic, 
expressions  are  often  seen.  Fibrillary  tremors  of  the  facial  muscles 
are  common. 

Motor  symptoms  are  always  present  and  are  of  the  greatest 
importance.  There  is  little  or  no  loss  of  muscular  power  except  a 
general  weakness  following  a  paretic  convulsion  and  an  increasing 
paralysis  diminishes  it.  There  is  early  seen  a  loss  of  ability  to  make 
several  movements  in  quick  succession,  like  opening  the   mouth. 


326  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

protruding  the  tongue  and  wrinkling  the  forehead.  The  performance 
of  single  movements  is  slow  and  clumsy,  while  the  carrying  out  of 
more  complicated  muscular  effort  early  becomes  an  impossibility. 

The  general  carriage  of  the  paretic  soon  becomes  lax  and  the  gait 
is  shuffling,  unsteady,  and  with  a  wide  base.  A  spastic  gait  is  also 
often  seen.  The  protrusion  of  the  tongue  is  usually  awkward  and 
jerky,  often  accompanied  by  movements  of  the  eyes  and  muscles  of 
the  face.  It  very  frequently  deviates  to  one  side  or  the  other  and 
a  fine  fibrillary  tremor  is  seen. 

The  most  striking  motor  disturbances,  however,  are  the  paretic 
convulsions.  These  convulsions  are  variously  stated  as  occurring  in 
from  30  to  90  per  cent,  of  cases.  They  are  probably  more  frequent 
in  men  than  in  women,  and  usually  occur  after  the  disease  has 
become  well  established  or  they  may  be  noted  as  one  of  the  earliest 
symptoms.  No  macroscopic  change  can  be  found  to  account  for 
them  but  they  are  probably  due  to  congestive  conditions  or  cir- 
cumscribed edemata  of  the  cortex. 

Certain  prodromal  symptoms  are  generally  noted,  such  as  more 
marked  dulness,  increased  clumsiness  of  movement,  or  even  uncon- 
sciousness. The  patient  frequently  is  seen  to  lean  far  to  one  side, 
finally  sinking  to  the  floor  when  the  convulsions  begin.  Usually 
simple  rhythmical  twitchings  are  observed,  although  jerking,  pitch- 
ing movements  are  not  rare.  Often  there  are  merely  twitchings  of 
the  face  muscles  with  nystagmus,  later  spreading  to  other  muscles 
of  the  body.  Sometimes  only  small  groups  of  muscles  are  affected 
such  as  those  of  the  arm,  the  attack  being  repeated,  perhaps  with 
slight  variations  as  many  as  one  hundred  times  in  twenty-four  hours, 
with  stupor  between  attacks. 

A  form  of  attack  which  occasionally  is  seen  resembles  an  apoplectic 
seizure,  whfle  sudden  death  is  not  infrequent.  One  feature  of  the 
paretic  attacks  is  their  usual  transitory  character.  The  recovery 
from  the  attack  generall}^  is  gradual  and  may  terminate  in  an  excited 
state.  There  is  almost  always  a  decrease  in  the  mental  capacity 
following  the  convulsions. 

The  sense  organs  often  show  a  hypersensitiveness  in  the  beginning 
of  the  disease  which  later  disappears,  the  senses  usually  being  dull. 
Word-deafness,  asymbolia  and  inability  to  recognize  substances  by 
the  sense  of  smell  are  often  noticed. 

The  sense  of  touch  is  usually  abnormal.  At  first  there  may  be 
sensations  of  itching,  burning,  tingling  and  may  be  the  only  symp- 
toms present  for  a  long  time. 

Later  in  the  course  of  the  disease  a  marked  lessening  of  the  pain 
sense  is  noted.  Often  the  paretic  may  receive  severe  burns  due  to 
his  insensibility  to  pain  and  the  self-infliction  of  wounds  by  biting, 
tearing  the  skin  with  the  finger-nails,  etc.,  is  not  rare. 


CLINICAL  HISTORY  327 

The  internal  organs  share  in  the  hypaigesia  and  the  paretic  may 
be  the  victim  of  severe  diseases  of  the  stomach,  gall-bladder,  etc., 
without  discomfort.  The  voice  of  a  paretic  early  loses  its  natural 
quality,  due  to  paralysis  of  the  vocal  cords,  and  is  more  or  less  monot- 
onous or  tremulous.  Changes  in  speech  are  of  the  utmost  importance 
and  consist  of  aphasia  and  difficulties  in  articulation.  Aphasia  is  fre- 
quent following  a  paretic  convulsion,  though  it  is  usually  transitory. 
Paraphasia  is  also  very  frequent  and  may  be  present  for  a  long  time. 
The  syllables  of  words  are  often  changed,  one  being  left  out  or 
repeated.  Those  who  have  been  acquainted  with  more  than  one 
language  often  jumble  the  words  of  different  languages  together. 
Inability  to  articulate  correctly  is  very  frequent,  and  difficult  words 
or  phrases  are  incorrectly  pronounced.  Thus  Theosiphus  is  called 
Teosipus.  While  the  patient  is  usually  unconscious  of  his  error,  he 
may  attempt  to  excuse  it. 

The  writing  of  a  paretic  presents  irregularities  which  are  com- 
parable to  his  speech  defects.  Letters  and  syllables  are  misplaced, 
repeated  and  omitted.  Little  or  no  attention  is  paid  to  spacing, 
while  the  writing  often  runs  off  the  page.  In  the  later  stages  of  the 
disease  complete  agraphia  is  seen.  Attempts  to  write  may  be  made, 
but  after  making  a  few  scrawling  lines  or  simply  a  blotch  on  the 
paper  he  gives  up  with  some  excuse. 

Pupillary  disturbances  are  noted  early  in  the  course  of  the  disease 
and  are  usually  most  striking.  The  most  characteristic  change  is  a 
distortion  of  the  outline  of  one  or  both  pupils.  The  opening  may  be 
eccentrically  located,  elliptical  or  flattened.  One  or  both  pupils  may 
be  pin-point  in  size  or  widely  dilated.  Irregularity  in  size  is  very 
frequent.  The  reaction  to  light  is  very  often  lost,  while  the  reaction 
to  accommodation  is  also  sometimes  absent.  Failure  to  react 
to  accommodation  without  loss  of  light  reaction  is  occasionally 
observed . 

Disturbances  of  superficial  and  deep  reflexes  are  generally  seen  in 
paresis.  As  a  rule  the  knee-jerks  are  markedly  exaggerated,  some- 
times differing  on  the  two  sides,  while  ankle-clonus  is  very  frequent. 
The  Achilles,  jaw,  elbow  and  wrist  reflexes  also  usually  are  exag- 
gerated, while  the  cremasteric  reflex  and  Babinski's  sign  are,  as  a 
rule,  positive.  In  a  certain  percentage  of  cases,  variously  estimated 
from  16  to  30,  the  knee-jerks  are  diminished  or  absent.  They  may 
later  become  exaggerated. 

Toward  the  end  of  the  disease  marked  rigidity  of  the  muscles 
with  contracture  is  noted.  These  contractures  are  of  a  most  severe 
type  almost  the  entire  musculature  of  the  body  participating  in  the 
process  until  neither  the  limbs  nor  the  head  can  be  moved. 

General  Symptoms. — The  general  appearance  of  a  paretic  is  that 
of  senility  with  wrinkled  skin,  gray  and  falling  hair,  tremors,  etc. 


328  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

At  first,  especially  during  the  excited  stage,  there  is  a  loss  in  weight, 
which  is  soon  followed  by  an  increase,  while  in  the  terminal  stages 
there  is  marked  emaciation.  The  appetite,  which  is  diminished  at 
first,  is  usually  voracious  later,  although  in  spite  of  this,  owing  to 
the  marked  altered  metabolism,  there  is,  as  noted  above,  loss  of 
weight. 

As  a  rule  there  is  no  increase  in  the  temperature  in  paresis,  except 
during  a  convulsion,  but  toward  the  end  a  subnormal  condition  is 
generally  observed.  Certain  trophic  disturbances,  such  as  bed-sores, 
which  are  very  prone  to  occur  in  the  terminal  stages,  herpes,  hema- 
tomata  of  the  ear,  etc.,  are  often  seen. 

A  striking  feature  of  paresis  is  the  frequency  of  fractures.  This 
undoubtedly  is  due  to  a  greater  fragility  of  the  bones,  and  often 
leads  to  false  accusations  of  attendants. 

The  sexual  strength  of  the  paretic,  which  is  often  increased  in  the 
beginning  of  the  disease  and  may  in  part  account  for  his  leud  con- 
duct, is  later  dminished  and  finally  entirely  lost. 

Bladder  symptoms,  both  paralysis  of  the  sphincter  with  inconti- 
nence and  retention,  are  noted.  The  condition  of  the  bowels  is 
often  most  distressing,  there  often  being  at  first  constipation  with 
impaction  and  distention,  while  later  there  is  incontinence  of  feces. 
The  whole  picture  of  paresis  in  the  terminal  stages,  both  mental  and 
physical,  is  one  of  the  most  repulsive  in  all  the  field  of  medicine. 

Cord  Substance. — Gummata  of  the  cord  are  exceedingly  rare 
and  may  originate  either  in  the  meninges  or  in  the  substance  of  the 
cord  itself.  The  symptoms  produced  will  depend  upon  their  location 
and  size. 

The  myelitis  following  syphilitic  arteritis  is  most  frequently  found 
in  the  dorsal  region.  Among  the  first  symptoms  noted,  in  fact  often 
the  first  symptom,  is  disturbance  of  the  bladder  function,  either 
incontinence  or  retention.  Other  symptoms  are  paresthesias,  para- 
plegia, usually  spastic,  disturbances  of  sensation,  either  in  all  of  the 
sensations  or  in  part  of  them.  Not  infrequently  the  temperature 
sense  is  the  only  one  not  disturbed.  As  a  rule  the  deep  reflexes  are 
increased,  while  the  superficial  reflexes  may  be  increased  or  dimin- 
ished.   Babinski's  sign  is  usualy  positive. 

When  the  lumbar  region  is  involved  there  is  a  flacid  paralysis  of 
the  legs  with  abolishment  of  both  superflcial  and  deep  reflexes. 
Bladder  symptoms  and  disturbances  of  sensation  are  similar  to 
those  in  dorsal  involvement.    Bed-sores  are  very  frequent. 

Involvement  of  the  cervical  region  is  marked  by  motor  and  sensory 
disturbances  in  all  four  extremities  with  perhaps  atrophy  of  the 
m^uscles  of  the  arms.  When  the  lower  segments  of  the  cervical  and 
the  upper  segments  of  the  dorsal  regions  are  involved  there  may  be 
afi'ections  of  the  sympathetic  with  contraction  of  the  pupil  of  the 


CLINICAL  HISTORY  329 

involved  side,  enopthalmus  and  suppression  of  perspiration  of  one- 
half  of  the  face. 

Tabes  Dorsalis. — Tabes  dorsalis  or  locomotor  ataxia,  as  is  paresis, 
is  now  known  to  be  a  true  syphilitic  disease  and  as  such  deserves 
most  careful  consideration. 

This  condition,  as  a  rule,  develops  somewhat  earlier  than  paresis, 
being  seen  most  frequently  between  the  fifth  and  tenth  years  follow- 
ing the  syphilitic  infection,  but  has  been  observed  as  early  as  ten 
months  after  the  chancre  and  as  late  as  thirty-five  years.  As  a  rule 
tabes  is  of  very  insidious  onset  and  is  extremely  slow  in  its  progress, 
its  course  occupying  ten,  twenty  or  even  thirty  years.  On  the  other 
hand,  however,  the  onset  of  tabes  may  be  abrupt  and  it  may  run  its 
course  to  a  fatal  termination  in  two  or  three  years. 

The  symptoms  of  tabes  are  in  the  aggregate  quite  constant,  while 
the  individual  symptoms  vary  within  a  wide  range.  They  may  be 
described  under  the  following  heads:  Sensory,  motor,  visual,  audi- 
tory, reflex,  visceral,  including  the  bones,  joints  and  muscles,  and 
trophic. 

Sensory  symptoms  are  both  subjective  and  objective,  the  former 
being  in  the  majority  of  cases  the  earliest  symptoms  of  the  disease. 

The  subjective  sensory  symptoms  consist  of  pains  of  varying  loca- 
tion and  intensity,  the  most  characteristic  ones  being  the  so-called 
lightning  or  lancinating  pains,  and  certain  paresthesias.  The  light- 
ning pains  are  most  frequently  noted  in  the  lower  extremities,  often 
beginning  in  the  great  toe  and  being  mistaken  for  gout.  They  may, 
however,  be  felt  in  the  face,  arms  or  trunk.  They  are  described  by 
the  patient  as  most  excruciating  in  character.  Their  duration  varies 
from  a  few  minutes  to  several  hours  or  even  days  and  can  be  relieved 
only  by  morphin.  There  is  usually  no  correspondence  of  the  pain 
with  the  distribution  of  the  nerve,  although  the  pain  may  sometimes 
simulate  sciatica.  These  pains  may  recur  with  rather  startling 
regularity  in  the  same  location,  and  if  beginning  early  in  the  course 
of  the  disease  they  may  disappear  later,  while  if  they  are  not  ob- 
served early  they  may  not  occur  at  all.  It  has  also  been  noted  that 
severe  pains  occurring  early  are,  as  a  rule,  followed  by  a  prolonged 
course  of  the  disease. 

Other  pains  of  a  less  severe  nature  but  more  permanent  are  noted. 
The  chief  of  these  is  the  so-called  girdle  pain  which  the  patient  de- 
scribes as  the  sensation  of  a  tight  belt  around  the  body.  It  generally 
is  narrow  in  extent,  may  be  located  at  any  level  of  the  trunk,  but  is 
sometimes  described  as  feeling  like  an  iron  jacket.  A  similar  pain 
on  the  arms  or  legs  is  often  noted,  and  described  as  feeling  like  a 
tight  bracelet  or  a  tightly  wound  rope  on  the  extremity.  These 
pains  may  last  for  long  periods  of  time,  even  years,  and  may  disappear 
only  to  recur  at  a  later  period. 


330  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

The  pains  referable  to  the  various  viscera  will  be  described  later. 

Certain  jMresthesias  such  as  numbness,  formication,  tingling, 
prickling,  the  sensation  of  walking  on  velvet,  as  if  cold  water  were 
running  over  the  body,  the  feeling  of  cobwebs  on  the  skin,  etc.,  are 
often  observed.  The  so-called  Hutchinson  mask,  the  sensation  of 
the  face  being  covered  with  a  mask  or  cobweb  is  not  rare. 

Of  the  objective  sensory  symptoms  the  most  frequent  is  analgesia 
which  affects  the  cutaneous  surface,  and  also  the  bones,  joints  and 
muscles.  Severe  injuries,  burns,  cuts,  bruises  and  even  fractures 
and  dislocations  are  unaccompanied  by  pain.  Analgesia  of  the  cuta- 
neous surface  is  found  in  areas  which  have  a  tendency  on  the  trunk 
and  extremities  to  bilateral  distribution,  while  on  the  head  the  dis- 
tribution is  usually  unilateral.  On  the  upper  extremities  the  most 
frequently  affected  areas  are  the  fingers  and  ulnar  border  of  the 
forearm.  The  sole  of  the  foot,  the  heel,  the  toes  and  the  inner  sur- 
faces of  the  thighs  are  the  favorite  locations  of  the  analgesia  in  the 
lower  extremities.  On  the  trunk  the  areas  most  often  affected  are 
over  the  pectoral  regions,  the  umbilicus,  the  inguinal  regions  and 
the  shoulders.  The  areas  of  analgesia  are  often  marked  by  borders 
of  hyperesthesia.  The  patient  is  frequently  unaware  of  his  affliction 
until  it  is  demonstrated  to  him,  and  shows  great  surprise  when  a  pin 
is  stuck  deeply  into  his  body  without  pain. 

Areas  of  hyperalgesia  are  also  common  but  are  less  symmetrically 
located  and  less  frequent.  Not  only  may  the  areas  be  more  sensi- 
tive to  such  pains  as  the  prick  of  a  needle  but  may  be  hyperalgesic 
to  heat  and  cold.  Often  these  areas  are  the  seat  of  the  lightning 
pains  and  appear  during  the  crises. 

Anesthetic  areas  are  very  frequently  observed  in  tabes.  The  most 
typical  is  the  so-called  tabetic  cuirass,  which  is  an  area  encircling  the 
trunk,  usually  three  or  four  inches  broad,  but  sometimes  occupying 
the  entire  length  of  the  trunk  and  often  associated  with  the  girdle 
pain.  Other  areas  of  anesthesia  are  sometimes  found  on  the  inner 
surfaces  of  the  arms  and  forearms,  the  ulnar  margins  of  the  hands, 
the  outer  margins  of  the  feet,  the  outer  sides  of  the  legs,  the  anterior 
and  internal  surfaces  of  the  thighs  and  in  the  perineum.  Not 
infrequently  there  are  alterations  in  the  pain  and  tactile  sense,  the 
individual  being  unable  to  tell  the  nature  of  a  pain,  perhaps  calling 
a  pin  prick  a  pinch.  The  pain  sense  may  also  be  retarded,  the  prick 
of  a  pin  being  felt  as  a  touch  immediately  and  later  (three  to  ten 
seconds)  felt  3,3  pain. 

A  striking  symptom  in  some  cases  is  an  impairment  of  stereognosis , 
the  patient  being  unable  to  distinguish  by  the  sense  of  touch  such 
objects  as  a  key  or  a  coin. 

Motor  symptoms  in  tabes  consist  of  ataxia,  which  may  be  more 
than  that  of  locomotion,  involuntary  movements,  and  paralyses. 


CLINICAL  HISTORY 


331 


The  ataxia  is  not,  as  a  rule,  an  early  symptom  of  tabes,  usually 
developing  after  sensory  symptoms  have  been  present  for  some  time. 
The  ataxia,  however,  may  be  the  first  symptom  to  call  the  attention 
of  the  patient  or  the  physician  to  the  true  nature  of  the  condition. 
It  is  usually  a  gradual  development,  the  patient  first  noting  that  he 
has  difficulty  in  ascending  or  descending  steps  or  walking  in  the 
dark.  He  soon  also  finds  it  difficult  to  stand  with  the  feet  close 
together  without  swaying  (Romberg's  sign).    Before  long  a  change 


Fig.  70. 


ait.     (Note  hyperextension  of  knee.) 


in  gait  is  noted,  the  feet  being  placed  on  the  ground  differently,  and 
he  walks  with  a  wide  base  and  finds  a  cane  of  assistance.  Gradually 
it  is  noticed  that  the  feet  are  raised  too  high,  are  placed  too  far  for- 
ward and  are  stamped  down  suddenly.  Later  standing,  even  with 
support,  becomes  impossible,  the  feet  slipping  out  in  front  of  him. 
Ability  properly  to  control  movements  of  the  feet  and  legs  while 
lying  in  bed  becomes  lost,  the  patient  throwing  the  foot  wide  of  the 
mark  when  told  to  touch  some  object  with  it. 

Ataxia  of  the  upper  extremities  may  not  occur,  may  follow  much 
later  that  of  the  lower  extremities  and  may  in  rare  instances  occur 
first.  This  is  noticable  in  such  movements  as  writing  and  grasping 
articles. 


332      >  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

The  involuntary  movements  of  tabes  consist  mainly  of  jerking  move- 
ments of  the  hmbs  or  portions  of  the  hmbs  as  a  thumb  or  finger,  and 
are  of  comparative  frequency.  They  may  occur  early  in  the  course 
of  the  disease  or  they  may  be  a  later  manifestation.  They  may 
occur  while  the  patient  is  asleep  or  while  he  is  awake  and  are  usually 
uniform  for  each  individual. 

The  ijaralyses  found  in  tabes  consist  of  monoplegias,  hemiplegia 
and  paraplegia,  paralysis  of  the  tongue  and  larynx,  facial  paralysis 
and  ptosis.  These  paralyses  are  due  to  organic  and  vascular  changes 
in  the  cerebrum  and  cord.  They  are  of  comparatively  infrequent 
occurrence  and  may  be  transitory  or  permanent. 

Visual  Symytoms. — Ptosis  has  been  mentioned  as  one  of  the 
symptoms  of  tabes  and  paralyses  of  the  muscles  of  the  eyeball  also 
occur,  the  external  rectus  being  most  often  affected. 

Anomalies  of  pupillary  reaction  are  found  in  the  vast  majority  of 
tabetics.  Of  these  the  so-called  Argyll-Robertson  pupil  is  the  most 
important.  This  phenomenon,  which  consists  of  a  loss  of  light 
reflex,  while  the  reaction  to  accommodation  remains  intact,  is  found 
in  from  50  to  70  per  cent,  of  cases.  It  is  usually  bilateral  but  may 
be  unilateral.  Other  pupillary  disturbances  are  inequality,  pin-point 
size,  increase  in  size,  irregularity  in  outline,  loss  of  accommodation 
and  absolute  iridoplegia.  Sluggishnes>:  of  the  pupils  with  slight 
irregularity  in  outline  or  inequalities  are  very  early  symptoms  of 
tabes,  while  the  other  pupillary  disturbances  are,  as  a  rule,  of  later 
occurrence.  Optic  atrophy  occurs  in  a  small  percentage  of  cases 
and  is,  as  a  rule,  of  early  development,  the  resulting  defect  in  vision 
or  blindness  often  being  the  first  symptom  to  lead  the  patient  to 
the  phj'^sician. 

Auditory  Symi^toms. — According  to  Murpurgo^  auditory  defects 
are  found  at  some  time  during  the  course  of  the  disease  in  80  per  cent, 
of  tabetics.  These  consist  of  recurring  sounds  like  the  ringing  of 
bells,  rushing  water,  whistles,  musical  sounds,  etc.  and  impairment 
of  hearing.  The  sounds  are  due  to  affections  of  the  cochlear  branch 
of  the  auditory  nerve,  while  the  impairment  of  hearing  may  be 
due  to  degeneration  of  the  auditory  nerve  or  to  abnormalities 
in  the  middle  or  external  ear. 

Reflex  Symptoms. — Diminished  or  absent  deep  reflexes,  especially 
the  knee-jerk,  is  one  of  the  earliest  and  most  frequent  symptoms  of 
tabes.  It  is  usually  bilateral  but  may  be  confined  to  one  side.  The 
superficial  reflexes  may  or  may  not  be  disturbed. 

Visceral  Symptoms. — The  most  important  and  frequent  of  the 
visceral  symptoms  are  those  referable  to  the  stomach.  The  so- 
called  gastric  crises,  which  are  of  sudden  onset,  may  occur  very  early 

1  Ar9h.  f.  Ohrenheilk.,  1890. 


CLINICAL  HISTORY  333 

in  the  course  of  tabes,  in  fact,  may  be  the  only  symptom  observed, 
the  patient  being  treated  for  other  types  of  gastric  disorder.  Pain 
is  the  most  conspicuous  feature  of  these  attacks,  is  located  in  the 
epigastrium,  just  beneath  the  xiphoid  cartilage,  and  may  radiate  in 
all  directions.  It  is  most  excruciating  in  character,  often  being  so 
severe  as  to  cause  unconsciousness.  Vomiting  also  occurs,  the 
attacks  being  frequent  and  uncontrollable.  It  may  or  may  not  be 
accompanied  by  straining.  It  occurs  regardless  of  the  presence  of 
food  in  the  stomach,  although  the  ingestion  of  even  a  very  small 
quantity  of  food  or  water  during  a  crisis  is  followed  by  its  immediate 
ejection.  The  vomitus  following  the  first  ejection  of  whatever 
undigested  food  is  present  is  soon  seen  to  consist  mainly  of  gastric 
mucous,  later  mixed  with  bile,  and  if  the  vomiting  is  long  continued, 
may  contain  blood. 

It  has  been  shown  that  in  the  beginning  of  the  attacks  a  hyper- 
acidity exists,  due  to  an  increase  in  hydrochloric  and  lactic  acids, 
which  is  diminished  throughout  the  attack.  The  gastric  crisis  may 
last  for  an  hour  or  for  days  or  even  weeks,  and  is  accompanied  by 
marked  prostration,  the  patient  appearing  as  if  suffering  from 
shock.  They  may  end  as  abruptly  as  they  began  with  a  cessation 
of  pain  and  a  desire  for  food.  One  crisis  may  be  the  only  one  experi- 
enced during  the  course  of  the  disease  but,  as  a  rule,  they  are  repeated, 
sometimes  daily,  but  usually  only  at  intervals  of  several  weeks  or 
months.  They  may  diminish  in  frequency  and  severity  as  the  dis- 
ease progresses  or  they  may  be  so  severe  as  to  cause  death. 

Intestinal  crises  are  of  rather  rare  occurrence,  are  characterized 
by  marked  diarrhea  but  without  pain.  Constipation  also  may 
occur.  Rectal  crises  are  more  frequent  and  are  accompanied  by 
most  intolerable  tenesmus,  and  the  passage  of  small  amounts  of 
bloody  mucous. 

The  bladder  is  the  seat  of  some  of  the  earliest  and  most  constant 
symptoms  of  tabes.  The  usual  condition  is  one  of  difficulty  in  start- 
ing urination  or  of  incontinence.  Vesical  tenesmus  of  a  most  dis- 
tressing character  is  also  sometimes  noted. 

Nephritic  crises  have  been  described,  but  may  be  due  to  true  renal 
colic. 

The  genital  organs  are  very  frequently  affected  in  tabes.  Diminu- 
tion of  the  sexual  appetite  and  even  impotence  are  observed  in  about 
50  per  cent,  of  the  cases  and  is  sometimes  preceded  by  an  excessive 
sexual  appetite.  Impotence  may  occur  very  early  in  the  course  of 
the  disease  or  may  only  appear  as  a  late  manifestation.  Diminution 
or  loss  of  the  cremasteric  reflex  and  the  so-called  virile  reflex  usually 
accompany  impotence  in  tabes.  The  testicle  is  sometimes  the  seat 
of  analgesia  and  is  often  accompanied  by  atrophy  of  the  organs. 
Clitoris  crises  may  occur  in  females. 


334  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

Laryngeal  crises  occur  quite  frequently  and  consist  of  spasms  of 
the  laryngeal  muscles.  The  symptoms  are  noisy  inspiration  and 
expiration  with  cough  and  usually  more  or  less  dyspnea  and  pain. 

The  hones  are  very  frequently  the  seat  of  spontaneous  fracture 
due  to  a  rarefication  and  decalcification.  The  most  frequently 
fractured  bones  are  the  femur,  the  tibia  and  fibula  and  the  ulna 
and  radius,  although  any  of  the  long  bones  may  easily  be  broken. 
The  bones  develop  this  condition  early  in  the  course  of  the  disease 
and  spontaneous  fractures  may  occur  before  any  symptoms  of  tabes 
have  been  noticed  or  they  may  occur  later. 

The  Joints. — The  so-called  Charcot's  joint,  which  sometimes 
occurs  in  tabes,  has  been  described  in  the  section  on  joint  affections. 
(See  pages  305  and  307.) 

The  muscles  in  tabes  usually  show  more  or  less  hypotonus  which 
corresponds  to  the  ataxia  of  the  limbs.  It  is  readily  appreciated  by 
the  ease  with  which  overextension  of  the  elbows,  knees  and  ankles,  and 
the  flexion  of  the  hip  and  abduction  of  the  thighs  may  be  produced. 

The  muscles  of  tabetics  also  in  some  cases  present  an  atrophy, 
the  onset  of  which  is  very  insidious  and  which  may  occur  early  in 
the  course  of  the  disease.  The  most  frequent  seats  are  the  foot  and 
leg  muscles  and  the  small  muscles  of  the  hands  and  the  forearm. 
The  resulting  deformities,  such  as  eqninovarus,  are  due  to  the 
atony  and  not  to  contracture.  The  wasting  and  flaccidity  of  the 
muscles  observed  late  in  the  course  of  the  disease  is  to  be  dis- 
tinguished from  this  atrophy. 

The  troyhic  symptoms  of  tabes  consist  mainly  of  certain  cutaneous 
lesions  such  as  herpes  zoster,  trophic  dermatoses,  hyperidrosis, 
anidrosis  and  hypertrophies  of  the  epidermis  of  the  extremities, 
and  are  of  more  or  less  rare  occurrence 

So-called  ferf orating  ulcer  is  more  frequently  found,  especially 
on  the  foot.  It  begins  as  a  callous  spot  on  the  sole  which  is  followed 
by  deep  ulceration  and  is  very  refractory  to  treatment. 

Decubitus  is  noted  only  in  the  terminal  stages  of  the  disease. 

Taboparesis,  as  the  name  implies,  is  a  combination  of  tabes 
dorsalis  and  general  paralysis.  While  tabetic  symptoms  may 
develop  in  an  individual  suffering  with  paresis  it  is  more  frequent 
for  the  symptoms  of  general  paralysis  to  develop  in  a  tabetic. 

Nerves. — Syphilis  of  the  cranial  nerves  is,  as  a  rule,  an  extension 
from  a  basilar  meningitis.  Any  of  the  cranial  nerves  may  be 
attacked  singly,  or,  which  is  more  frequent,  several  that  are  in  close 
anatomical  relation  become  involved  together.  The  resulting  symp- 
toms wil  naturally  depend  upon  the  nerves  affected,  thus,  the 
involvement  of  the  optic  nerve  will  cause  more  or  less  disturbance 
of  vision,  even  blindness,  choked  disk,  etc.,  while  involvement  of 
the  oculomotor,  which  is  probably  the  most  frequently  affected  of 


DIAGNOSIS  335 

the  cranial  nerves,  will  cause  paralysis  of  the  ocular  muscles  sup- 
plied by  this  nerve. 

Neuralgias  due  to  syphilis  are  of  comparatively  frequent  occur- 
rence, usually  being  observed  early  during  the  course  of  the  disease^ 
but  may  be  late  manifestations.  The  trifacial,  the  sciatic,  the  cer- 
vical and  brachial  plexes,  and  the  intercostals  are  most  often 
involved.  Syphilitic  neuritis  and  jwlyneuritis  are  rarely  observed 
and  the  symptoms  do  not  differ  from  the  symptoms  seen  in  these 
conditions  due  to  other  causes. 

Diagnosis. — The  diagnosis  of  syphilis  of  the  nervous  system  can 
in  many  cases  be  made  with  considerable  certainty  upon  clinical 
evidence  alone,  but  to  the  author's  mind  such  a  diagnosis  is  rarely 
justifiable  without  the  evidence  of  laboratory  procedures,  especially 
the  examination  of  the  spinal  fluid.  In  certain  cases  of  tabes  and 
paresis  in  the  terminal  stages,  however,  the  spinal  fluid  may  be 
entirely  negative  to  laboratory  tests,  in  which  cases  the  diagnosis 
must  rest  upon  the  history  and  clinical  evidence. 

Meninges. — Syphilitic  meningitis  must  be  differentiated  from 
meningitis  due  to  other  etiological  factors,  especially  that  due  to 
the  tubercle  bacillus  and  the  Diplococcus  intracellularis.  This  can, 
as  a  rule,  be  accomplished  by  the  more  acute  course  of  the  tubercular 
and  epidemic  forms  of  meningitis,  as  well  as  the  presence  of  fever 
which  is  rarely  seen  in  the  syphilitic  form.  However,  in  most  cases 
it  is  necessary  to  resort  to  lumbar  puncture  and  examination  of 
the  spinal  fluid  to  determine  the  true  nature  of  the  affection. 

Arteries. — Syphilitic  arteritis  of  the  brain  with  the  resulting 
encephalitis,  which  is  usually  accompanied  by  more  or  less  meningitis, 
causes  symptoms  which  may  be  mistaken  for  a  variety  of  conditions. 
The  most  important  of  these  is  paresis  and  in  some  cases  the  differ- 
ential diagnosis  may  be  most  difficult.  The  usual  insidious  onset 
of  paresis,  the  progressive  dementia  and  paralysis,  the  complete 
alteration  of  personality  and  disorientation  will  in  the  majority  of 
cases  serve  to  distinguish  this  disease  from  the  more  acute,  irregular 
course  of  syphilitic  arteritis.  Nevertheless  the  diagnosis  of  syphilitic 
arteritis  to  the  exclusion  of  paresis  should  not  be  made  without 
recourse  to  examination  of  the  spinal  fluid.     (See  Chapter  VIL) 

Even  with  this  evidence  a  diagnosis  may  sometimes  be  impos- 
sible and  the  final  verdict  must  rest  upon  an  observation  of  a  con- 
siderable period  of  time  and  the  effects  of  specific  therapy. 

Syphilitic  arteritis  of  the  central  nervous  system  must  also  be 
differentiated  from  arteriosclerosis,  uremic  poisoning,  viultiple 
sclerosis,  hysteria,  and  chronic  alcoholism. 

Arteriosclerosis  usually  occurs  later  in  life  than  specific  arteritis 
but  the  clinical  picture  may  be  so  similar  that  only  laboratory 
evidence  can  clear  the  diagnosis. 


336  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

Uremic  poisoning  is  accompanied  by  disease  of  the  kidneys, 
which  will  be  manifest  by  examination  of  the  urine. 

Multiple  sclerosis  may  be  manifested  by  symptoms  resembling 
syphilitic  arteritis  and  the  two  conditions  sometimes  can  be  differ- 
entiated only  by  laboratory  procedures. 

Hysteria,  especially  if  it  occurs  in  a  syphilitic,  may  present 
difficulties  of  diagnosis  which  can  be  cleared  up  only  by  lumbar 
puncture  and  spinal  fluid  examination. 

In  chronic  alcoholism  evidences  of  the  recent  ingestion  of  this 
drug  are  usually  observed,  and  after  its  eft'ects  have  had  time  to 
wear  off  the  true  nature  of  the  condition  will,  as  a  rule,  be  manifest. 
However,  more  or  less  lasting  symptoms  may  be  present  and  the 
resort  to  laboratory  procedures  may  be  necessary. 

Brain  Substance. — Gummata  of  the  brain  substance  cannot 
be  differentiated  from  non-syphilitic  tumors  upon  clinical  evidence 
alone.  The  history  may  be  of  value  and  laboratory  procedures 
should  be  instituted.  The  Wassermann  test  upon  the  blood  may  or 
may  not  be  positive,  and  too  much  reliance  should  not  be  placed 
upon  it,  as  it  is  possible  for  a  non-luetic  tumor  of  the  brain  to  develop 
in  an  individual  suffering  from  syphilis,  but  without  central  nervous 
system  involvement.  If  the  gumma  is  deeply  embedded  in  the 
brain  substance,  the  spinal  fluid  will,  as  r.  rule,  yield  negative  results, 
although  the  Wassermann  test  may  be  positive.  The  final  diagnosis 
may  have  to  rest  upon  the  result  of  specific  therapy,  although  even 
this  may  be  of  no  avail,  as  not  all  gummata  yield  to  treatment. 

Paresis. — In  the  majority  of  cases  of  general  paralysis  the  clinical 
picture  is  quite  characteristic  and  when  positive  laboratory  evidence 
is  added  to  this,  especially  the  gold  chloride  test,  mistakes  should 
rarely  be  made.  In  no  other  syphilitic  condition  are  laboratory 
procedures  of  more  importance  and  to  the  author's  mind  a  diagnosis 
of  paresis  should  rarely  be  made  without  them.  Certainly  such  a 
diagnosis  should  never  be  made  upon  psychic  symptoms  alone. 

As  stated  above,  encephalitis  due  to  syphilitic  involvement  of 
the  arteries  of  the  brain  may  simulate  paresis  and  the  differential 
diagnosis  has  been  discussed. 

The  mental  symptoms  of  paresis  may  be  mistaken  for  many  other 
abnormal  psychic  states  such  as  manic-depressive  insanity,  paranoia, 
hysteria,  senile  dementia,  alcoholic  deterioration,  etc.,  and  often  a 
correct  diagnosis  can  only  be  reached  by  resort  to  spinal  puncture. 

The  paretic  convulsion  must  be  differentiated  from  epilepsy  and 
convulsions  due  to  uremic  poisoning  and  diabetes. 

In  epilepsy  the  history  of  seizures  for  years  before  mental  symp- 
toms began  will,  as  a  rule,  serve  to  distinguish  it  from  paresis,  while 
an  examination  of  the  urine  in  uremic  poisoning  and  in  diabetes 
will,  as  a  rule,  clear  up  the  diagnosis. 


DIAGNOSIS  337 

Cord  Substance. — Gummata  of  the  spinal  cord,  though  rare, 
are  to  be  differentiated  from  other  tumors  of  non-specific  origin. 

The  history  and  a  positive  Wassermann  reaction  upon  the  spinal 
fluid  will  clear  up  the  diagnosis.  A  history  of  lues  cannot  by  any 
means  always  be  obtained  and  the  Wassermann  may  be  negative 
(see  page  156),  so  that  the  final  diagnosis  may  of  necessity  rest 
upon  a  therapeutic  test.  Even  this  test  may  prove  negative,  as 
gummata  of  the  cord  as  well  as  gummata  of  the  brain  do  not  always 
yield  to  specific  therapy. 

Myelitis  due  to  syphilitic  involvement  presents  no  symptoms 
which  are  pathognomonic  and  which  may  not  occur  in  non-luetic 
spinal  cord  disease.  The  main  conditions  which  must  be  differ- 
entiated from  syphilitic  myelitis  are  spinal  neurasthenia,  tumors, 
multiple  sclerosis,  hysteria  and  myelitis  due  to  compression  from 
tubercular  caries  of  the  vertebrce,  and  while  the  history  may  be  of  value 
the  diagnosis  must,  as  a  rule,  rest  upon  laboratory  evidence,  especially 
lumbar  puncture,  and  therapeutic  procedures. 

Tabes  Dorsalis. — The  diagnosis  of  a  fully  developed  case  of 
tabes  dorsalis  rarely  presents  much  difficulty,  but  in  the  early  course 
of  the  disease  before  ataxia  has  developed  it  may  be  confused  with 
many  other  conditions.  The  various  visceral  crises  and  the  light- 
ning and  girdle  pains  are  quite  frequently  ascribed  to  other  causes, 
especially  if 'occurring  before  other  symptoms.  This  fact  but  serves 
to  emphasize  the  importance  of  a  thorough  examination  of  all 
patients  presenting  themselves  for  diagnosis,  as  very  early  in  the 
course  of  tabes  pupillary  anomalies  and  disturbances  of  reflexes 
will  be  found.  Behr^  emphasizes  the  fact  that  pupillary  disturbance, 
especially  only  partial  failure  of  the  iris  to  contract  to  light,  may  be 
found  even  years  before  other  symptoms.  He  states  that  this  some- 
times cannot  be  detected  without  the  use  of  the  ophthalmoscope. 

The  repetition  of  a  gastric  or  other  crisis  or  of  the  lightning  or 
girdle  pains  should  at  once  arouse  suspicion. 

Later  in  the  course  of  tabes  the  most  important  disease  from 
which  it  is  to  be  differentiated  is  multiple  neuritis.  In  the  latter 
condition,  the  more  rapid  development,  the  absence  of  the  Argyll- 
Robertson  pupil,  girdle  pains  and  laboratory  evidence  of  syphilis, 
as  well  as  a  history  of  some  toxic  condition  such  as  diphtheria, 
typhoid,  lead  poisoning  or  aleoholism  will  serve  to  establish  a 
diagnosis. 

It  must  be  remembered  that  there  is  a  certain  small  percentage 
of  cases  of  tabes,  according  to  Kaplan,^  7  per  cent.,  in  which  all 
laboratory  evidence  of  syphilis  is  negative.  In  these  cases  the  diag- 
nosis must  rest  upon  the  history  and  clinical  evidence. 

1  Med.  Klin.,  1914.  x,  p.  1842. 

2  Serology  of  Nervous  and  Mental  Diseases,  Philadelphia  and  London,  1914,  p.  136. 

22 


338  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

Tahoparesw. — The  diagnosis  of  taboparesis  depends  upon  the  same 
factors  as  the  diagnosis  of  tabes  and  paresis  occurring  separately. 

It  is  sometimes  extremely  difficult  in  cases  which  are  frankly 
tabetic  to  determine  whether  or  not  a  condition  of  involvement  of 
the  brain  substance  also  exists.  The  obtaining  of  a  typical  paretic 
curve  in  the  colloidal  gold  test  would  be  very  significant. 

Nerves. — There  is  nothing  characteristic  in  syphilitic  involve- 
ment of  the  nerves  and  the  diagnosis  must  rest  upon  the  history, 
evidence  of  syphilis  of  other  localities,  laboratory  procedures  and 
the  result  of  specific  therapy. 

Prognosis. — The  prognosis  of  syphilis  of  the  nervous  system  was 
formerly  almost  always  bad,  but  with  the  institution  of  more 
modern  therapy  the  outlook   is  much  less  gloomy  than  heretofore. 

The  importance  of  early  diagnosis  of  syphilitic  involvement  of 
the  nervous  system  must  be  emphasized.  As  with  all  syphilis, 
so  especially  with  syphilis  of  the  nervous  system,  the  earlier  the 
condition  is  recognized,  the  better  will  be  the  prognosis.  It  may  be 
said,  however,  that  where  there  has  been  actual  destruction  of  ner- 
vous tissue  no  hope  of  regeneration  can  be  entertained,  that  the  best 
which  can  be  expected  is  to  stop  the  advance  of  the  process. 

Meninges. — The  prognosis  of  complete  recovery  from  the 
syphilitic  meningitis  seen  early  in  the  course  of  the  disease  probably 
is  better  than  that  of  any  other  syphilitic  condition  of  the  nervous 
system.  With  the  institution  of  vigorous  antisyphilitic  treatment 
most  cases  become  normal  both  clinically  and  from  a  laboratory 
standpoint  in  a  surprisingly  short  time. 

Syphilitic  meningitis  occurring  later  in  the  course  of  the  disease, 
during  the  second  or  third  year,  is  more  serious,  although  even  this 
meningitis  may  be  completely  cured  by  proper  therapy.  Meningitis 
of  the  convexity  is  more  refractory  to  treatment  than  basilar  men- 
ingitis. This  is  especially  true  if  the  basilar  meningitis  is  limited 
to  one  side  of  the  brain.  Syphilitic  meningitis  of  the  spinal  cord 
is  also  quite  amenable  to  treatment. 

Arteries. — The  prognosis  of  syphilitic  arteritis  is  worse  than 
that  of  meningitis.  The  earlier  the  condition  is  recognized,  however, 
the  better  will  be  the  prognosis.  If  the  diagnosis  is  made  before 
the  arteries  have  become  obliterated,  intensive  antisyphilitic  treat- 
ment may  arrest  the  process  and  the  patient  return  to  normal. 
If,  however,  obliteration  has  taken  place  and  destruction  of  nerve 
tissue  has  occurred,  the  best  that  can  be  hoped  for  is  to  stop  the 
advance  of  the  disease.  The  symptoms  depending  upon  destruc- 
tion of  tissue  will  remain,  although  to  a  certain  extent  the  lost 
functions  may  be  taken  over  by  the  normal  portions  of  central 
nervous  system.  Involvement  of  the  basilar  artery  is  almost 
always  fatal. 


PROGNOSIS  339 

Brain  Substance. — Gummata  of  the  brain  substance  quite 
frequently  yield  to  antisyphilitic  treatment;  however,  some  cases 
are  most  refractory.  In  these  cases  surgical  interference  has  been 
tried  with  some  measure  of  success. 

Paresis. — The  prognosis  in  paresis  is  the  most  gloomy  of  all 
syphilitic  processes,  and  even  since  the  establishment  of  the  direct 
etiological  relationship  of  the  Treponema  pallida  to  this  condition 
and  the  advent  of  modern  methods  of  treatment  few  cases  of  com- 
plete recovery  have  been  reported  and  most  of  these  are  open  to 
some  doubt  as  to  the  correctness  of  the  diagnosis.  Nevertheless 
this  unfavorable  outlook  should  not  deter  the  physician  from  car- 
rying out  all  the  therapeutic  means  at  his  disposal,  with  the  hope 
that  the  process  may  be  arrested.  The  fact  must  not  be  lost  sight 
of,  however,  that  remissions,  even  of  several  years'  duration,  have 
been  observed  and  must  not  be  mistaken  for  cure. 

In  the  majority  of  cases,  however,  remissions,  if  occurring  at  all, 
are  of  short  duration  and  the  disease  goes  on  to  a  rather  speedy 
fatal  termination.  According  to  Kraepelin^  nearly  one-half  of  all 
cases  die  in  the  course  of  the  first  two  years.  This  author  tabulates 
the  year  of  the  disease  in  which  deaths  occurred  in  224  cases  as 
follows : 


1st 

2d 

3d 

4th 

5th 

6th 

7th 

8th 

9th 

10th 

14th 

51 

63 

52 

41 

22 

4 

5 

2 

2 

1 

1 

Of  104  cases  of  paresis  at  the  Arkansas  State  Hospital  for  Nervous 
Diseases,  the  majority  of  whom  were  observed  by  the  author, 
48  are  living  at  the  present  time,  (1915)  with  residence  in  the 
institution  as  follows: 

Less  than  one  year 29 

Between  one  and  two  years 15 

Between  two  and  three  years 4 

Of  the  56  who  are  dead,  19  died  during  the  first  three  months  of 
residence  in  the  hospital,  8  during  the  second  three  months,  5  during 
the  third  three  months,  3  during  the  fourth  three  months,  16 
during  the  second  year,  4  during  the  third  year,  and  1  during  the 
fourth  year. 

Cord. — Gummata  of  the  substance  of  the  cord  may  yield  to  anti- 
syphilitic  remedies,  or  if  these  fail,  surgical  intervention  may  bring 
results.  The  myelitu  following  arteritis  of  the  cord  is  usually  most 
refractory  to  treatment,  the  majority  of  cases  going  on  to  a  fatal 
termination.  Usually  the  most  that  can  be  hoped  for  is  to  arrest 
the  process. 

1  General  Paresis,  New  York,  1913,  p.  99. 


340  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

Tabes  Dorsalis. — Since  the  institution  of  modern  methods  of 
treatment  the  prognosis  in  tabes  has  become  more  hopeful  and 
even  cases  of  long  standing  may  yield  in  a  remarkable  manner. 
It  must  be  said,  however,  that  those  cases  which  are  early  recog- 
nized and  show  the  greatest  activity  of  the  syphilitic  process, 
that  is,  those  with  positive  laboratory  findings  are  the  most  amenable 
to  treatment.  Cases  in  which  marked  degeneration  has  taken  place, 
cannot,  of  course,  be  restored  to  normal  but  the  process  may  be 
stopped,  and  at  least  the  subjective  symptoms,  the  lightning  pains 
and  crises  may  be  relieved.  This  in  itself  constitutes  a  distinct 
victory,  as  probably  no  suffering  in  all  the  field  of  human  ills  is  more 
intense.  It  must  be  remembered  that  many  cases  of  tabes  progress 
to  a  certain  stage,  the  process  halting  even  without  treatment  and 
remaining  stationary  for  long  periods  of  time,  even  years. 

Taboparesis. — The  prognosis  of  taboparesis  is  most  grave,  as 
practically  all  cases  go  on  to  a  fatal  termination.  It  has  been  noted 
that  sometimes  when  tabetic  symptoms  develop  in  a  paretic  the 
mental  condition  improves,  and  on  the  other  hand,  when  paretic 
symptoms  occur  in  a  tabetic  there  may  be  a  diminution  of  the 
ataxia. 

Nerves. — The  prognosis  of  syphilitic  involvement  of  the  cranial 
nerves,  which  occurs  in  association  with  specific  basilar  meningitis, 
is  practically  the  same  as  the  prognosis  of  the  meningitis,  although 
if  degeneration  has  taken  place  the  outlook  is  very  unfavorable. 

Syphilitic  neuralgia,  especially  that  occurring  early  in  the  course 
of  the  disease,  is  very  amenable  to  treatment,  most  cases  quickly 
being  cured  upon  the  administration  of  specifics. 

The  prognosis  of  neuritis  and  polyneuritis  will  depend  upon  the 
extent  of  the  process  and  the  prognosis  of  the  syphilis  itself. 

Mortality. — Mott^  gives  the  following  table  regarding  the  mor- 
tality of  cerebral  syphilis: 

Fournier.     Hjellmann.  Naunyn. 

Cured i  i  24  probable 

Improved J  5  49  t 

Death    .......      e    -  2  ^ 

10  (treatment  no  influence) 

The  mortality  of  148  cases  of  cerebral,  spinal,  and  cerebrospinal 
syphilis  seen  by  Nonne^  is  shown  in  the  following  table : 

Died     .  .  16  cases  =   10.8  per  cent  \    ^^  ^^^^^    ^  3^^           ^^^^ 

Unimproved  .  30  cases  =  20 . 3  per  cent.  J 

Improved  .  30  cases  =20.3  per  cent.  \      g  cases    =68.9  per  cent. 

Recovered  .  72  cases  =  48 . 6  per  cent.  J 

1  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  iv,  p.  482. 

2  Syphilis  and  the  Nervous  System,  Philadelphia  and  London,  1913,  p.  163. 


TREATMENT  341 

According  to  Hoppe,  as  quoted  by  Kraepelin/  32.8  per  cent,  of 
paretic  men  and  18.5  per  cent,  of  paretic  women  die  during  convul- 
sions, whicli  may  occur  at  nearly  any  time  during  the  course  of  the 
disease.  Pneumonia,  following  the  aspiration  of  food  or  saliva, 
especially  during  convulsions,  is  the  most  common  cause  of  death. 
Septicemia  and  fat  embolism  from  bed-sores,  pyelitis  or  cystitis 
also  not  infrequently  cause  death.  Some  paretics  die  from  suffo- 
cation during  vomiting  or  stuffing  their  mouths  with  food  and 
aspirating  a  portion  into  the  larynx,  and  finally  in  those  who  escape 
the  dangers  described,  death  from  cardiac  failure  terminates  a 
severe  marasmus. 

Treatment. — Syphilis  of  the  nervous  system  is  caused  by  the  same 
organism  that  causes  syphilis  of  other  portions  of  the  body,  never- 
theless the  treatment  of  syphilis  of  the  nervous  system  presents 
problems  which  differ  in  many  respects  from  the  treatment  of  other 
syphilitic  involvement.  The  ideal  which  it  is  desirable  to  attain 
in  the  treatment  of  any  case  of  syphilis  is  completely  to  rid  the  body 
of  the  invading  organisms  and  to  restore  to  normal  the  portions  of 
the  body  involved.  In  the  case  of  syphilis  of  the  nervous  system  this 
may  be  undertaken  by  the  administration  of  specific  remedies  by 
the  ordinary  methods  as  in  any  case  of  syphilis  with  the  hope  that 
these  remedies  will  be  carried  to  and  destroy  the  organisms,  and 
by  the  direct  administration  of  specifics  to  the  parts  involved.  To 
these  may  be  added  certain  general  measures  as  outlined  for  the 
treatment  of  all  syphilis,  and  symptomatic  treatment.  All  cases  of 
syphilis  of  the  nervous  system  should  be  most  vigorously  treated 
with  specifics  in  the  same  manner  as  syphilis  of  any  other  portion  of 
the  body.  Added  to  this,  in  cases  of  involvement  of  the  cerebro- 
spinal axis,  specific  medication  directly  administered  to  the  parts 
involved  should  be  undertaken. 

Probably  the  first  investigator  to  treat  syphilis  of  the  nervous 
system  by  intraspinal  injection  was  Schachmann,^  who,  in  1901, 
treated  4  cases  by  the  injection  1  c.c.  of  a  1  per  cent,  solution  of 
mercury  benzoate.  One  case  of  syphilitic  myelitis  is  reported  in 
detail.  This  patient  received  twenty-three  injections  in  twenty- 
five  days,  showing  marked  improvement.  The  first  injection 
caused  restlessness,  slight  rise  in  temperature  and  insomnia,  but 
by  the  fifth  injection  no  untoward  symptoms  were  ob- 
served. 

Karsley,  according  to  Smith,^  in  1910,  advocated  intraspinal 
irrigations  with  mercuric  chloride  solution  for  syphilis  of  the 
nervous  system. 

1  General  Paresis,  New  York,  1913,  p.  100. 

2  Bull,  de  la  Soc.  med.  des  hop.  de  Paris,  October  24,  1901. 

3  Jour.  Am.  Med.  Assn.,  1915,  Ixiv,  p.  1563. 


342  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

The  work  of  Swift  and  Ellis^  on  the  intraspinal  injection  of 
salvarsanized  serum,  however,  was  the  first  to  arouse  any  consider- 
able attention,  and  since  the  publication  of  their  investigations 
numerous  workers  have  applied  their  method  and  it  has  stimulated 
others  into  devising  similar  procedures,  so  that  today  intraspinal 
treatments  and  intracranial  have  taken  a  permanent  place  in  the 
therapy  of  syphilis  of  the  nervous  system. 

The  method  of  Swift  and  Ellis  consists  of  administering  a  large 
dose  of  salvarsan  or  neosalvarsan  intravenously,  and  one  hour  after 
administration  to  withdraw  by  venipuncture  40  c.c.  of  blood.  This 
is  allowed  to  clot,  after  which  it  is  centrifugalized  and  the  clear 
serum  pipetted  off.  The  next  day  12  c.c.  of  the  serum  are  diluted 
with  18  c.c.  of  normal  salt  solution  which  make  a  40  per  cent,  solu- 
tion. This  is  heated  in  the  water-bath  at  56°  C.  for  half  an  hour, 
after  which  it  is  injected  intraspinally  by  gravity  following  the 
withdrawal  by  lumbar  puncture  of  a  sufficient  quantity  of  spinal 
fluid  to  reduce  the  pressure  to  30    mm. 

Wechselmann,^  in  1913,  reported  the  intraspinal  injection  of 
neosalvarsan  into  two  paretics  and  also  into  two  children  with 
congenital  syphilis,  without  any  injurious  effects. 

Marinesco^  injected  thirteen  patients  intraspinally  with  neosal- 
varsan, each  receiving  5  mg.  in  4  c.c.  of  solution.  Severe  unpleasant 
symptoms  appeared  immediately  in  ten  of  them,  while  eight  devel- 
oped permanent  bladder  disturbance.  This  author  also  reports 
the  intraspinal  injections  of  serum  from  patients  with  so-called 
secondary  syphilis  following  treatment  with  salvarsan.  In  these 
cases  some  beneficial  results  were  noted. 

Robertson'*  treated  paretics  with  intraspinal  injections  of  serum 
of  patients  with  secondary  syphilis  withdrawn  on  the  third  day 
after  the  intravenous  injection  of  salvarsan.  Serum  from  the 
patients  themselves  one  hour  after  the  intravenous  injection  of 
salvarsan  also  was  used. 

Marie  and  Levaditi^  treated  paretics  with  intraspinal  injections 
of  neosalvarsan  in  doses  of  0.005  to  0.04  gram. 

Wile^  advocated  the  technic  of  Ravaut  which  he  describes  as 
follows: 

A  6  per  cent,  solution  of  neosalvarsan,  which  is  hypertonic,  is 
employed.  Each  drop  contains  3  mg.  of  the  drug  and  is  prepared 
by  dissolving  the  contents  of  a  0.3  gram  ampule  of  neosalvarsan 
in  5  c.c.  of  sterile  freshly  distilled  water.    The  dose  to  be  admin- 

1  New  York  Med.  Jour.,  1912,  xcvi,  p.  53. 

2  Deutsch.  Med.  Wchnschr.,  1912,  xxxviii,  p.  1446. 

3  Ztschr.  f.  diatet.  u.  physik.  Therap.,  1913,  xvii,  p.  194. 

*  Edinburgh  Med.  Jour.,  1913,  x,  p.  428. 

s  Bull,  et  mem.  Soc.  M6d.  d.  h6p.  de  Paris,  1913,  Series  3,  xxxvi,  p.  675. 

*  Jour.  Am.  Med.  Assn.,  1914,  Ixii,  p.  1165. 


TREATMENT 


343 


istered,  which  varies  from  3  to  12  mg.  (1  to  4  drops),  is  placed  in 
a  syringe  accurately  graduated  in  drops.  A  spinal  puncture  is 
performed  with  a  needle  into  which  the  syringe  fits  and  after  a 
few  drops  of  spinal  fluid  have  escaped  the  syringe  is  attached 
and  the  fluid  allowed  to  flow  into  the  syringe  barrel  where  it  mixes 
with  the  neosalvarsan.  The  fluid  and  drug  are  now  forced  into  the 
spinal  canal  by  gentle  pressure  on  the  plunger  of  the  syringe.  Slight 
suction  is  then  made  with  the  plunger  to  withdraw  a  small  amount 
of  fluid  and  wash  out  the  needle,  following  which  it  is  reinjected  and 
the  needle  withdrawn.  The  patient  is  then  placed  in  the  Trendel- 
enburg position  in  which  he  remains  for  one  hour. 


Fig.  71. — Method  of  intraspinal  injection. 


A  distinct  advance  in  the  preparation  of  salvarsanized  serum  for 
intraspinal  injection  has  been  proposed  by  Ogilvie.^  His  method 
consists  of  withdrawing  about  50  c.c.  of  blood  from  the  patient 
without  previous  intravenous  treatment.  This  is  centrifugalized 
immediately  at  a  high  rate  of  speed  which  throws  the  fibrin  and 
cellular  elements  down,  and  the  serum  is  pipetted  off.  To  15  c.c. 
of  this  is  directly  added  the  salvarsan  in  the  dose  which  is  to  be 
used.  The  salvarsan  is  prepared  as  for  intravenous  injection  with 
freshly  distilled  and  boiled  water,  the  total  quantity  being  made 
up  so  that  each  40  c.c.  contains  0.1  gram  of  the  drug  or  each  c.c, 
0.25  mg.  Ogilvie  cautions  against  adding  an  excess  of  sodium 
hydroxide  when  preparing  the  salvarsan  solution.    He  also  states 

1  Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  p.  1936. 


344  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

that  the  temperature  of  the  salvarsan  and  the  serum  should  be  the 
same  when  the  two  are  mixed.  The  dose  recommended  by  Ogilvie 
is  from  0.25  to  0.5  mg.  for  repeated  injections,  although  he  has  given 
as  high  as  4  mg.  After  adding  the  salvarsan  and  gently  shaking 
to  thoroughly  mix  the  two  the  serum  is  placed  in  a  thermostat  at 
37°  C.  for  forty-five  minutes,  then  in  a  thermostat  at  56°  C.  for 
thirty  minutes.  Ogilvie  insists  that  it  should  be  administered  as 
soon  as  possible  after  preparation  and  under  no  circumstances 
should  it  be  injected  if  more  than  three  hours  old. 

Wile^  recently  has  modified  his  technic  for  intraspinal  medica- 
tion, employing  salvarsan  instead  of  neosal-varsan.  His  method  is 
to  attach  the  barrel  of  a  40  c.c.  Luer  syringe  to  the  spinal  puncture 
needle  after  a  successful  puncture  by  means  of  about  eight  inches 
of  rubber  tubing.  About  10  c.c.  of  the  spinal  fluid  are  allowed  to 
flow  into  the  barrel  of  the  syringe  by  lowering  the  latter  below  the 
level  of  the  puncture  site.  The  salvarsan  is  a  freshly  prepared, 
neutralized  solution  of  0.1  gram  in  30  c.c.  of  water  and  the  amount 
used  0.1  c.c.  (approximately  2  drops),  corresponding  to  I  mg., 
is  carefully  dropped  into  the  barrel  of  the  syringe  and  stirred  into 
the  fluid  by  means  of  a  sterile  glass  rod.  The  salvarsanized  fluid 
is  now  allowed  to  flow  into  the  spinal  canal  by  gravity  by  raising  the 
barrel  of  the  syringe  above  the  level  of  the  puncture  site. 

Byrnes^  suggested  the  intraspinal  injection  of  mercurialized  serum 
prepared  from  human  blood  serum  by  adding  a  solution  of  bichloride 
of  mercury  in  a  manner  similar  to  that  described  for  the  prepara- 
tion of  mercurialized  serum  for  intravenous  injection.  This  is  used 
in  doses  of  0.0013  gram  (5^0-  grain)  to  0.0026  gram  {-jq  grain)  and 
is  administered  by  gravity. 

Recently  a  similar  preparation  prepared  from  horse  serum  has 
been  placed  upon  the  market  and  has  given  satisfactory  results 
in  the  hands  of  the  author,  although  he  prefers  to  prepare  the  serum 
himself  from  human  blood. 

Intracranial  injection  of  specifics  in  the  treatment  of  syphilis 
of  the  nervous  system  has  been  practised  by  several  workers. 
Wardner^  treated  five  patients  by  intracranial  injection  of  salvar- 
sanized serum  prepared  after  the  technic  of  Swift  and  Ellis.  The 
patient  is  prepared  for  operation,  anesthetized  with  ether,  and  a 
trephine  hole  bored  as  nearly  as  possible  over  the  precentral  gyrus. 
When  the  dura  is  exposed  20  c.c.  of  spinal  fluid  are  withdrawn 
by  lumbar  puncture.  This  relieves  the  tension  which  is  noted  in 
the  dura  and  permits  the  respiratory  pulsations  of  the  membrane 
to  be  plainly  seen.     By  means  of  a  30   c.c.  Luer  syringe  and  an 

1  Jour.  Lab.  and  Clin.  Med.,  1915,  i,  p.  119. 

2  Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  p.  2182. 
'  Am.  Jour.  Insan.,  1915,  Ixxi,  p.  459. 


TREATMENT  345 

ordinary  small  caliber  salvarsan  needle,  bent  upon  itself  at  about  a 
quarter  of  an  inch  from  the  point,  connected  by  about  18  inches 
of  rubber  tubing,  30  c.c.  of  the  previously  prepared  salvarsanized 
serum  are  injected  subdurally  by  gravity.  Wardner  states  that  the 
trephine  opening  should  be  not  less  than  2  cm.  in  diameter  for  the 
safe  introduction  of  the  needle. 

Hamill^  reports  two  cases  treated  by  the  intracranial  injection 
of  neosalvarsan.  A  lumbar  puncture  is  performed  and  about  6 
c.c.  of  spinal  fluid  withdrawn.  Following  this  a  Neisser-Polock 
puncture  is  made  8  cm.  above  the  orbital  arch,  2.5  mg.  are  care- 
fully weighed  out,  dissolved  in  5  c.c.  of  spinal  fluid  and  injected 
subdurally  through  the  cranial  puncture,  one-half  on  either 
side. 

Hammond  and  Sharpe^  recently  have  reported  the  intraventric- 
ular injection  of  salvarsanized  serum  and  neosalvarsan  in  paretics. 
Their  technic  is  as  follows:  The  patient  is  etherized  and  a  small 
skin  flap,  slightly  larger  than  the  trephine  used  is  made  a  little  in 
front  of  the  bregma  and  2.5  cm.  from  the  sagittal  sinus.  A  button 
of  bone  1.5  cm.  in  diameter  is  removed  and  an  incision  made  in 
the  dura.  A  blunt  slender  canula  is  introduced  at  a  point  free 
from  underlying  vessels  and  passed  downward  and  a  little  backward 
into  the  lateral  ventricle.  The  head  of  the  table  is  lowered,  and  from 
10  to  20  c.c.  of  fluid  allowed  to  escape.  The  head  of  the  table  is 
then  raised  and  the  serum  allowed  to  flow  slowly  into  the  ventricle 
by  gravity  from  a  funnel  through  a  rubber  tube  attached  to  the 
canula,  after  which  the  canula  is  removed  and  the  scalp  wound 
sutured.  In  subsequent  injections  a  general  anesthetic  is  not  re- 
quired as  the  brain  is  not  sensitive  and  the  scalp  may  be  opened 
over  the  trephine  opening  under  novocaine. 

The  rationale  of  the  subdural  treatment  oi  syphilis  of  the  cere- 
brospinal axis  is,  of  course,  to  bring  the  specific  drug  into  as  direct 
contact  as  possible  with  the  tissues  involved. 

Certain  syphilographers  have  objected  to  the  treatment  on  the 
ground  that  it  is  not  necessary,  that  the  salvarsan  or  neosalvarsan 
reaches  these  areas  as  readily  following  intravenous  administration 
as  following  subdural  injection.  The  majority  of  investigators, 
however,  have  shown  that  the  spinal  fluid  following  intravenous 
administration  of  the  arsenicals  contains  little  or  no  arsenic. 

Lorenz,^  working  with  sodium  cacodylate,  found  that  the  spinal 
fluid  contained  no  arsenic  following  the  intravenous  administra- 
tion of  small  doses.  With  doses  of  1  gram,  however,  traces  of  arsenic 
were  found  in  the  spinal  fluid  one  hour  after  administration. 

1  Illinois  Med.  Jour.,  1915,  xxvii,  p.  204. 

2  Jour.  Am.  Med.  Assn.,  1915,  Ixv,  p.  2147. 

3  Med.   Rec,   1912,   Ixxii,  p.   185. 


346  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

Camp^  administered  0.6  gram  of  salvarsan  intravenously  and 
performed  spinal  puncture  at  varying  periods  from  15  minutes  to 
40  hours  after  injection.  In  only  one  instance  was  arsenic  found  in 
the  spinal  fluid.  This  was  in  a  case  of  so-called  secondary  syphilis, 
in  which  the  spinal  puncture  was  performed  15  hours  after  the 
injection  of  the  salvarsan. 

Engman,  Buhman,  Gorham,  and  Davis^  performed  spinal  punc- 
ture on  four  paretics,  withdrawing  10  c.c.  of  spinal  fluid  immediately, 
after  which  a  full  dose  of  neosalvarsan  was  administered  intra- 
venously. In  two  of  the  cases  spinal  puncture  was  performed  again 
in  48  hours  and  in  the  other  two  in  98  hours.  The  examination  of 
the  fluids  for  the  presence  of  arsenic  by  the  Gutzeit  and  Marsh 
tests  were  negative  in  all  cases. 

Sicard  and  Bloch^  were  unable  to  find  arsenic  in  the  spinal  fluid 
of  patients  following  either  the  intramuscular  or  subcutaneous 
administration  of  0.4  gram  of  salvarsan.  However,  traces  of  arsenic 
were  found  in  the  spinal  fluid  of  one  patient  two  hours  after  the 
intravenous  administration  of  0.4  gram  of  salvarsan. 

Hall'^  administered  neosalvarsan  intravenously  to  five  patients, 
performing  spinal  puncture  one  and  a  half  hours,  six  hours,  and 
twenty-four  hours  following  injection  without  finding  arsenic  in 
the  spinal  fluid.  Salvarsan  was  injected  intravenously  into  six 
patients,  the  spinal  fluid  showing  arsenic  only  in  two  cases  after 
twenty-four  hours. 

Swift^  states  that  with  the  pooled  fluids  up  to  100  c.c.  withdrawn 
the  day  following  the  intravenous  injection  of  salvarsan  almost 
uniformly  negative  results  were  obtained,  and  that  when  arsenic 
was  found  it  was  in  such  small  quantities  it  could  not  be  estimated. 

Contrary  to  the  above-mentioned  observations,  Benedict^  found 
from  an  analysis  of  four  specimens  of  spinal  fluid  withdrawn  twenty- 
four  hours  following  the  intravenous  injection  of  0.4  gram  of  sal- 
varsan, free  arsenic  in  "about  one-sixth  to  one-tenth  the  concen- 
tration in  the  whole  blood." 

As  Swiff  pertinently  remarks  in  view  of  the  negative  results 
obtained  by  most  investigators,  these  findings  are  hard  to  explain, 
unless  in  Benedict's  case  the  permeability  of  the  meninges  and 
choroid  plexus  was  markedly  impaired  by  the  syphilitic  process. 

Further  evidence  that  solutions  injected  subcutaneously  and 
into  the  blood  stream  do  not  reach  the  tissues  of  the  cerebrospinal 
axis  nearly  as  readily  as  when  injected  subdurally  is  furnished  by 

1  Jour.  Nervous  and  Mental  Diseases,  1912,  xxxix,  p.  809. 

2  Jour.  Am.  Med.  Assn.,  1913,  lix,  p.  735. 

3  Bull.  et.  mem.  Soe.  med.  d.  hop  de  Paris,  1911,  3  S.,  xxxi,  p.  664. 

4  Jour.  Am.  Med.  Assn.,  1915,  Ixiv,  p.  1384.  'Ibid.,  1915,  Ixv,  p.  209. 
*  Cited  by  Sachs,  Strauss  and  Kaliski,  Am.  Jour.  Med.  Sc,  1914,  cxlviii,  p.  693. 
•^Jour.  Am.  Med.  Assn.,  1915,  Ixiv,  p.  1384. 


TREATMENT  347 

Woolsey.^  His  investigations  also  show  the  rationale  of  intra- 
cranial injections  in  certain  cases.  This  worker  found  that  repeated 
subcutaneous  injections  of  trypan  blue  over  a  period  of  several 
days  and  intensely  staining  all  other  tissues  of  the  body  failed  to 
reach  the  central  nervous  system  except  in  exceedingly  small  quan- 
tities. Intra-arterial  injections  resulted  in  intense  generalized 
blue  color  of  the  other  tissues  which  was  in  marked  contrast  to  the 
creamy  whiteness  of  the  central  nervous  system  with  only  slight 
tinting  of  the  cranial  dura  and  ventricular  plexus.  Injections  into 
the  jugular  vein  were  always  followed  by  intense  staining  of  the 
tissues  with  the  exception  of  the  central  nervous  system.  On  the 
other  hand,  subarachnoid  lumbar  injections  of  trypan  blue  resulted 
in  marked  staining  of  the  meninges  of  the  cord  up  to  the  level  of 
the  cervical  enlargement  above  which  the  intensity  of  the  staining 
diminished  to  the  foramen  magnum,  while  the  cranial  meninges 
showed  a  distinct  deep  blue,  in  places  they  also  showed  many  areas 
hardly  more  deeply  stained  than  in  the  intravascular  injections. 
The  substance  of  the  cord  to  a  depth  of  ^  to  1  mm.  below  the  surface 
was  stained  a  distinct  blue,  while  the  brain  substance  showed  no 
such  staining. 

Campbell  has  shown  that  when  trypan  blue  is  injected  subdurally 
through  a  trephine  hole  above  the  tentorium  cerebelli  the  cerebral 
cortex  as  well  as  the  whole  cerebrospinal  axis  is  stained,  and  that 
when  injected  through  lumbar  puncture  only  the  cord  and  brain 
stem  are  stained,  while  the  cortex  cerebri  remains  unstained.  He 
therefore  concludes  that  there  is  a  slight  flow  of  the  spinal  fluid 
from  the  brain  toward  the  spinal  canal  and  that  an  ebb  and  flow 
occurs  in  the  fluid  between  the  subarachnoid  space  in  the  base  of 
the  cranium  and  the  spinal  subarachnoid  space  depending  upon  the 
variations  in  the  quantity  of  the  intracranial  blood. 

Certain  syphilographers,  who  have  found  fault  with  the  Swift- 
Ellis  method  of  treatment  have  based  their  objections  upon  the  low 
arsenic  content  of  the  blood  serum  withdrawn  at  the  specified 
time  following  the  intravenous  injection  of  salvarsan.  Thus, 
Sachs,  Strauss  and  Kaliski^  state  that  Benedict  was  able  to  find 
but  0.00004  gram  to  0.0001  gram  of  metallic  arsenic  in  20  c.c.  of 
whole  blood  forty-five  minutes  after  injection. 

As  Swift'*  has  pointed  out,  however,  this  represents  from  0.12 
to  0.3  mg.  of  salvarsan  which  corresponds  rather  closely  to  his 
figures  which  averaged  0.016  mg.  per  c.c.  of  serum,  and  is  approxi- 
mately the  amount  recommended  by  Ogilvie^  as  safe  for  repeated 

1  Jour.  Nervous  and  Mental  Diseases,  1915,  xlii,  p.  477. 

2  Brit.  Med.  Jour.,  1914,  ii,  p.  577. 

3  Am.  Jour.  Med.  Sc,  1914,  cxlviii,  p.  693. 

*  Jour.  Am.  Med.  Assn.,  1915,  Ixiv,  p.  1384.  ^  ibid.,  1914,  Ixiii,  p.  1936. 


348  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

injection  according  to  his  method.  The  higher  figure  also  is  approxi- 
mately the  amount  recommended  by  Wile.^  The  objection  to  the 
use  of  serum  salvarsanized  in  vivo  is  not,  therefore,  found  in  its  low 
arsenic  content,  but  in  the  variable  amount  of  arsenic  present. 

It  has  been  suggested  that  the  favorable  results  obtained  in  the 
treatment  of  syphilis  of  the  nervous  system  by  the  method  of  Swift 
and  Ellis  might  be  due  to  other  factors  than  the  arsenic  content  of 
the  serum.  For  example,  it  has  been  thought  that  the  injection  of 
the  serum  rendered  the  meninges  more  permeable  so  that  the  sal- 
varsan  circulating  in  the  blood  was  enabled  to  reach  the  tissues  of 
the  nervous  system  more  readily.  Stillman  and  Swift^  have  shown, 
however,  that  such  is  not  the  case.  It  has  also  been  stated  that  the 
presence  of  the  salvarsan  in  the  patient's  body  for  a  period  of  time 
may  cause  the  formation  of  certain  unknown  substances  which  are 
present  in  the  serum  and  act  favorably  upon  the  syphilitic  process. 
It  is  for  this  reason  that  Ogilvie^  incubates  the  serum  at  body  tem- 
perature for  forty-five  minutes. 

In  consideration  of  any  therapeutic  measure,  however,  two 
factors,  aside  from  its  rationale,  must  be  taken  into  account,  namely, 
its  practical  value  and  its  untoward  effects  if  any  occur.  The  efficacy 
of  subdural  injections  of  specifics  in  the  treatment  of  syphilis  of  the 
cerebrospinal  axis  is  attested  by  numerous  investigators;  in  fact, 
with  very  few  exceptions  all  workers  who  have  reported  upon  the 
use  of  this  method  of  treatment  have  commented  favorably.  Swift 
and  Ellis*  report  in  detail  10  cases  (8  of  tabes  and  2  of  cerebrospinal 
syphilis)  in  which  marked  improvement  was  noted  following  intra- 
spinal treatment  according  to  their  technic.  Swift^  later  summarized 
the  results  of  the  treatment  of  34  tabetics,  3  paretics,  and  2  tabo- 
paretics.  Of  the  34  tabetics,  in  whom  observation  extended  over 
at  least  one  year,  3  received  intraspinal  treatment  alone,  while  the 
remainder  received  intravenous  treatment  as  well.  In  25  cases,  or 
73  per  cent,  negative  Wassermann  reactions  were  obtained  with 
1  c.c.  of  spinal  fluid,  while  in  14  of  these  cases  the  reaction  was 
negative  with  2  c.c.  In  8  cases  the  Wassermann  was  negative  with 
1  c.c.  and  positive  with  2  c.c.  A  number  showed  negative  reactions 
for  from  one  and  a  half  to  two  and  a  half  years.  Two  of  the  3  paretics 
treated  died,  while  the  third  who  responded  well  both  clinically 
and  biologically  while  under  treatment  relapsed  twice  when  treat- 
ment was  discontinued.  The  2  taboparetics  responded  only  slightly 
and  relapsed  when  treatment  was  stopped. 

1  Jour.  Lab.  and  Clin.  Med.,  1915,  i,  p.  119. 

2  Jour.  Exper.  Med.,  1915,  xxii,  p.  286. 

3  Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  p.  1936.  / 
"Arch.  Int.  Med.,  1913,  xii,  p.  331. 

s  Jour.  Am.  Med.  Assn.,  1915,  Ixiv,  p.  1384. 


TREATMENT  349 

Wile^  reported  in  detail  15  cases  treated  by  the  Ravaut  method. 
Of  these  2  died,  7  were  markedly  improved,  both  subjectively  and 
in  the  objective  findings  in  the  spinal  fluid;  3  paretics  who  received 
only  a  single  injection  showed  no  improvement,  1  showed  improve- 
ment after  a  single  injection  followed  by  relapse  and  no  subsequent 
treatment:  While  his  cases  are  too  few  to  draw  any  but  tentative 
conclusions  from  his  experience,  it  would  seem  that  cases  with 
cerebrospinal  syphilis,  other  than  tabes  or  paresis,  show  much  more 
improvement  than  when  one  or  both  of  the  latter  conditions  are 
present. 

Ogilvie-  in  his  original  communication  states  that  in  all  cases 
treated  by  his  method  there  was  biological  improvement  and  in 
the  majority  a  concomitant  clinical  improvement.  He,  however, 
states  that  it  was  too  early  to  draw  definite  conclusions  as  to  the 
permanency  of  the  results.  In  a  later  paper  Ogilivie^  summarizes 
the  results  of  the  treatment  of  15  cases,  in  13  of  which  there  was 
a  complete  disappearance  of  all  subjective  manifestations,  while 
the  objective  signs  showed  more  or  less  improvement  for  an  average 
period  of  one  year.  One  showed  moderate  improvement  only, 
while  1  failed  utterly  to  respond  to  the  treatment. 

Wile*  reports  the  result  of  the  treatment  of  15  cases  by  his  method, 
using  salvarsan,  in  all  but  2  of  which  definite  objective  improvement 
was  noted  in  the  spinal  fluid,  and  a  very  marked  improvement  in 
the  subjective  symptoms  in  the  majority  of  cases.  Three  cases 
passed  from  observation  but  in  the  remaining  12,  relapses  did  not 
occur.  The  most  marked  results  were  obtained  in  early  brain  and 
cord  syphilis,  although  in  tabes  encouraging  results  were  noted. 

Byrnes^  treated  32  cases  of  syphilis  of  the  nervous  system  with 
his  mercurialized  serum  witTi  very  encouraging  results,  the  most 
improvement  being  seen  in  tabes  and  meningomyelitis,  although 
some  cases  of  paresis  were  distinctly  benefited.  BjTnes  does  not 
give  his  results  in  detail  but  concludes  that  the  mercurialized  serum 
is  equally,  if  not  more,  efficacious  than  salvarsanized  serum. 

Numerous  other  workers  have  reported  favorably  upon  the 
intraspinal  treatment  of  syphilis  of  the  nervous  system.  Paresis 
seems  the  most  resistent  to  this  type  of  treatment,  which  from  the 
location  of  the  organisms  is  to  be  expected,  although  some  very 
encouraging  results  have  been  obtained  in  early  cases  of  this 
condition. 

In  contrast,  however,  to  the  almost  brilliant  results  obtained  by 
most  investigators  Sachs,  Strauss  and  Kaliski^  state  that  the  intra- 

1  Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  p.  137.  2  Ibid.,  p.  1936. 

3  Med.  Rec,  1915,  Ixxxvii,  p.  1062. 

*  Jour.  Am.  Med.  Assn.,  1914,  Ixiii.  p.  137.  s  ibid.,  p.  2182. 

6  Am.  Jour.  Med.  Sc,  1914,  cxlviii,  p.  693. 


350  SYPHILIS  OF   THE  NERVOUS  SYSTEM 

spinous  treatment  possesses  no  advantage  over  the  intravenous. 
Such  a  statement  is  hard  to  understand,  for,  while  the  time  has 
been  too  short  since  the  introduction  of  this  method  to  draw 
absolutely  definite  conclusions  concerning  the  permanency  of  the 
improvement  usually  recorded,  there  is  enough  favorable  evidence 
of  its  superiority  over  other  methods  to  warrant  its  use  in  some  form 
in  all  cases  of  syphilis  of  the  cerebrospinal  axis. 

The  results  of  intracranial  injections  in  syphilis  of  the  nervous 
system  have  in  some  instances  been  more  brilliant  than  those 
obtained  by  intraspinal  injections. 

Wardner^  in  the  treatment  of  five  cases  of  paresis  by  intracranial 
injections  of  salvarsanized  serum  reports  complete  remissions  in 
two  cases  after  two  treatments,  which  have  remained  unchanged 
for  one  and  two  months  repectively.  One  case  after  three  treat- 
ments had  a  remission  with  slight  impairment  of  apperception  and 
judgment.    Two  cases  showed  no  improvement  after  one  injection. 

Hammond  and  Sharpe^  state  that  while  two  of  their  three  patients 
injected  intraventricularly  showed  "definite  changes  for  the  better 
a  statement  of  the  progress  at  this  early  date  would  be  valueless." 
However,  these  writers  by  experiments  with  trypan  blue  have 
shown  that  the  distribution  of  the  dye  in  the  cortex,  following 
intraventricular  injections  is  much  more  extensive  than  that 
following  subdural  injections  either  intracranially  or  intraspinally. 

The  most  suggestive  result  thus  far  obtained  is  found  in  the 
case  of  Gordon.^  This  patient  with  syphilis  of  fifteen  years'  standing 
showed  both  cerebral  and  spinal  symptoms  which  had  resisted 
intravenous  injections  of  salvarsan.  Seven  intraspinous  injections 
of  auto-salvarsanized  serum  relieved  and  finally  removed  the  cord 
symptoms  but  had  no  effect  on  a  most  severe  headache  which  was 
the  most  marked  cerebral  symptom.  This  headache,  however, 
was  relieved  completely  by  the  subdural  intracranial  injection  of 
30  c.c.  of  auto-salvarsanized  serum  following  spinal  puncture  and 
the  withdrawal  of  30  c.c.  of  spinal  fluid.  After  a  period  of  four 
months,  during  which  the  patient  reported  regularly  each  week 
for  inspection,  no  recurrence  of  pain  was  noted. 

Untoward  Effects. — Certain  untoward  effects  following  intra- 
spinal medication  have  been  reported.  Thus  Swift  and  Ellis'* 
state  that  frequently  there  is  a  certain  amount  of  pain  in  the  legs, 
commencing  a  few  hours  after  the  injection.  This  they  state  is 
noticed  more  often  in  tabetics  than  in  patients  with  so-called 
cerebrospinal  syphilis. 

More  serious  results,  however,  follow  the  Revaut  technic  and 

1  Am.  Jour.  Insan.,  1915,  Ixxi,  p.  459. 

2  Jour.  Am.  Med.  Assn.,  1915,  Ixv,  p.  2147.  ^  ibid.,  p.  154. 
4  Arch.  Int.  Med.,  1913,  xii,  p.  286. 


TREATMENT  351 

such  symptoms  as  pain  in  the  legs  and  hips,  nausea  and  vomiting 
and  suppression  of  the  urine  frequently  are  noted.  Gordon^  reports 
a  case  of  tabes  which  previously  had  received  an  intraspinal  injection 
after  the  method  of  Swift  and  Ellis  with  very  gratifying  results  and 
no  untoward  effects,  which  one-half  hour  after  the  injection  of  6 
mg.  of  neosalvarsan  by  Revaut's  method  developed  severe  pains 
in  the  lower  limbs,  and  during  the  same  day  vomiting  which  con- 
tinued for  five  days.  Retention  of  urine  and  incontinence  of  feces 
developed  and  all  symptoms  continued  without  relief.  On  the 
fifth  day  small  erythematous  patches  developed  on  the  glans  penis, 
scrotum  and  sacrum  which  soon  became  larger  and  distinctly  gan- 
grenous and  his  condition  gradually  grew  worse  until  he  died. 

A  most  unfortunate  accident  occurred  in  the  Los  Angeles  County 
Hospital  in  March,  1914,^  when  eight  deaths  followed  the  intra- 
spinal injection  of  neosalvarsanized  serum.  The  serum  was  pre- 
pared by  adding  freshly  dissolved  neosalvarsan  in  doses  of  1,  2, 
and  3  mg.  to  5  c.c.  of  serum  and  heating  to  54°  C.  for  half  an  hour. 
After  remaining  on  ice  for  twenty-four  hours  they  were  injected 
intraspinally.  The  autopsy  of  one  of  the  patients  showed  "  a  some- 
what congested  spinal  cord  with  marked  distention  of  the  blood- 
vessels and  softening  of  the  posterior  columns."  This  unfortunate 
occurrence  must  have  been  due  to  changes  in  the  neosalvarsan  occur- 
ring during  the  time  the  serums  remained  on  ice. 

Lewinsohn^  reports  a  severe  and  nearly  fatal  arrest  of  respiration 
occurring  twenty-four  hours  following  the  intraspinal  injection  of 
6  c.c.  of  a  solution  of  0.15  gram  of  neosalvarsan  in  300  c.c.  of  saline. 

No  more  marked  untoward  symptoms  have  been  reported  fol- 
lowing the  intraspinal  injection  of  salvarsanized  serum  prepared 
after  Ogilvie's  method,  or  the  mercurialized  serum  prepared  after 
BjTues's  method  than  following  the  intraspinal  injection  of  the 
Swift  and  Ellis  salvarsanized  serum.  In  fact,  Byrnes'*  states  that 
in  general  the  reactions  are  not  so  severe. 

It  was  the  severity  of  the  reactions  following  the  Ravaut  technic 
which  led  Wile^  to  discard  this  method  and  adopt  the  new  one 
reported.  Using  the  later  technic  Wile  states  that  the  only  untoward 
symptom  noted  was  a  slight  amount  of  darting  pain  for  a  few  hours 
following  injection  which  invariably  disappeared  in  twenty-four 
hours.    This  was  observed  only  in  tabetics. 

The  author  used  the  Swift-Ellis  method  of  intraspinal  medication 
exclusively  until  the  Byrnes  method  was  described,  which  he  adopted 
at  once.    Later  the  Ogilvie  method  was  employed  instead  of  the 

1  Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  p.  1851. 

2  Ibid.,  1914,  Ixii,  pp.  861  and  957. 

3  Deutsch.  med.  Wchnschr.,  1915,  xli,  p.  248. 

*  Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  p.  2182. 
6  ,Jour.  Lab.  and  Clin.  Med.,  1915,  i,  p.  119. 


352  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

Swift-Ellis  method  and  recently  the  Wile  technic  of  injection  of 
salvarsan  has  been  employed  in  a  few  cases. 

The  only  untoward  symptoms  observed  in  over  two  hundred 
injections  have  been  slight  pains  in  the  legs  and  back,  which  usually 
were  controlled  by  asperin.  In  one  instance  only  was  it  necessary 
to  administer  morphin. 

A  large  percentage  of  the  cases  treated  were  paretics  of  the 
advanced  hospital  type  which  showed  little  or  no  improvement. 
A  considerable  number  were  tabes  cases  which  came  to  Hot  Springs 
for  treatment  and  after  one  or  two  injections  without  marked 
clinical  improvement  refused  further  injections  or  went  home. 

One  case  of  syphilitic  meningitis  which  the  author  has  been  able 
to  follow  consistently  deserves  mention. 

Case  1. — Male,  aged  thirty-two  years,  married;  travelling  sales- 
man. Contracted  syphilis  seven  years  ago.  Treated  with  "mixed 
treatment"  intermittently  for  two  years.  Nervous  manifestations 
such  as  dizziness,  weakness  and  numbness  in  the  legs  occurred  in 
summer  of  1913,  at  which  time  he  received  two  doses  of  salvarsan 
intravenously  followed  by  improvement.  In  January,  1914,  the 
nervous  symptoms  returned,  at  which  time  there  was  difficulty  of 
speaking  and  walking,  slight  retention  of  urine  and  also  some  loss 
of  memory.  On  January  18,  1914,  an  examination  showed  the 
following:  Right  pupil  dilated  and  irregular  in  outline,  left  pupil 
normal  in  size,  both  pupils  react  sluggishly  to  light  and  accom- 
modation. Eye-grounds  normal.  Lower  tendon  reflexes  markedly 
exaggerated,  ankle-clonus  and  Romberg  sign  positive. 

Blood:  Wassermann,  negative.  Spinal  fluid  Wassermann 
+  +  +  +.    Cell  count  99;  globulin  +  +• 

This  patient  was  thoroughly  mercurialized  with  the  succinimide 
and  given  potassium  iodide  until  symptoms  of  iodism  appeared, 
after  which  he  received  three  intravenous  injections  of  0.6  gram  of 
salvarsan  ten  days  apart  followed  by  intraspinal  injections  of  sal- 
varsanized  serum  after  the  method  of  Swift  and  Ellis.  Spinal  fluid 
removed  at  the  time  of  the  last  injection  showed  26  cells  per 
c.mm.;  globulin  +;  Wassermann  +  +;  while  the  clinical  symptoms 
had  improved  remarkably. 

At  this  time  the  patient  was  forced  to  return  to  his  home  but 
reported  again  for  treatment  in  June.  The  same  course  of  treat- 
ment was  carried  out  and  the  spinal  fluid  collected  at  the  time  of 
the   third    injection   showed    12    cells   per    c.mm.;    globulin    — ; 

Wassermann  -\ with  1  c.c. 

Again  in  September  the  same  course  of  treatment  was  carried 
out  and  spinal  fluid  showed  6  cells  per  c.mm.;  globulin  ^; 
Wassermann  —  with  1  c.c.  The  blood  Wassermann  remained  con- 
stantly negative.     The  clinical  symptoms  were  completely  cured 


TREATMENT  353 

with  the  exception  of  a  slight  exaggeration  of  the  lower  tendon 
reflexes.  In  December,  1915,  the  patient  showed  no  clinical 
symptoms  of  his  former  disease  but  refused  spinal  puncture. 

Other  Treatment  of  Syphilis  of  the  Nervous  System. — In  syphilis 
of  the  nervous  system,  as  with  syphilis  of  other  regions  of  the  body, 
other  treatment  than  specific  and  general  sometimes  is  indicated. 

In  syphilitic  meningitis  the  headache  may  require  the  coal-tar 
derivatives  or  it  may  be  so  severe  as  to  require  opiates,  although 
it  usually  will  yield  to  some  form  of  specific  medication. 

The  treatment  of  syphilitic  arteritis,  aside  from  the  administra- 
tion of  specifics,  consists  of  treating  the  symptoms.  A  hemiplegia 
occurring  suddenly  with  symptoms  of  apoplexy  should  be  treated 
with  absolute  rest,  ice  packs  to  the  head  and  liquid  diet.  Massage, 
hydrotherapy  and  electricity  may  be  used  to  advantage  in  treating 
the  permanent  paralysis. 

Gummata  of  the  brain  will  require  treatment  other  than  specific 
according  to  the  location,  number  and  size  and  the  symptoms 
produced.  Numerous  investigators  have  practised  surgical  pro- 
cedures on  brain  gummata  with  more  or  less  success.  If  a  certain 
diagnosis  of  brain  gumma  has  been  made  and  it  does  not  yield  to 
specific  medication,  and  further,  if  the  tumor  is  in  an  accessible 
location,  surgery  should  be  tried. 

The  treatment  of  paresis  other  than  specific  and  general  must  be 
symptomatic,  and  usually  is  best  carried  out  in  a  hospital,  especially 
if  an  excited  mental  state  exists.  Greatly  excited  paretics  may 
require  the  continuous  bath  or  the  administration  of  sedatives. 
Careful  watching  to  prevent  injuries  to  the  patient  and  others 
is  necessary. 

Often  the  paretic  will  refuse  food  and  tube  feeding  may  become 
necessary,  while,  especially  in  the  later  stages,  he  will  have  to  be 
cleansed  frequently.  The  prevention  of  decubitus  is  sometimes 
difficult  but  frequent  bathing,  the  use  of  alcohol  and  the  care  and 
cleanliness  of  the  bed  and  changing  the  position  of  the  patient 
frequently  will  in  the  majority  of  cases  prevent  this  complication. 
The  treatment  of  bed-sores  in  paretics  after  they  have  once  formed 
is  most  difficult.  The  use  of  the  continuous  bath  and  the  applica- 
tion of  antiseptic  powders  may  result  in  a  cure. 

The  paretic  convulsion,  according  to  Kemmler,^  should  be  treated 
by  packing  the  head  in  ice  and  in  severe  seizures  the  administra- 
tion of  amyl  hydrate  either  per  rectum  or  hypodermically. 

The  results  of  gummata  of  the  cord  and  myelitis  will  require 
symptomatic  treatment.  As  far  as  the  author  is  aware  surgery 
has  not  been  resorted  to  in  the  treatment  of  cord  gummata. 

1  Cited  by  Kraepelin:  General  Paresis,  New  York,  1913,  p.  196. 
23 


354  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

The  treatment  of  tabes  aside  from  the  most  vigorous  antisyphilitic 
medication  and  general  treatment  consists  of  symptomatic  measures 
and  the  attempt  to  restore  lost  coordination.  The  application  of 
cautery  and  cold  in  various  forms  such  as  ice,  douche,  etc.,  to  the 
spine  have  been  advocated,  but  are  of  questionable  value. 

The  lightning  and  other  pains  of  tabes  sometimes  are  so  severe 
as  to  require  morphin,  although  hot  and  cold  applications  or  the 
coal-tar  derivatives  may  control  them.  Resection  of  the  posterior 
roots  of  the  seventh  to  the  tenth  dorsal  nerves  for  the  control  of 
gastric  crises  has  been  successfully  practised. 

Vesical  weakness  may  sometimes  be  overcome  by  exercises  which 
strengthen  the  pelvic  floor,  such  as  separating  and  adducting 
the  knees  against  resistence  while  lying  on  the  back  as  well  as  by 
massage  of  the  perineal  muscles.  Cystitis  must  be  guarded  against 
and  is  best  prevented  by  the  administration  of  urotropin. 

Treatment  of  tabetic  arthropathies  is  of  little  or  no  avail.  Cer- 
tain supporting  and  fixation  apparatus  may  be  of  service  in  enabling 
the  patient  to  walk. 

In  attempting  to  restore  lost  coordination  certain  exercises  are 
of  the  utmost  value.  FrankeP  describes  two  types  of  exercises, 
those  performed  by  the  patient  in  bed  and  those  performed  out 
of  bed. 

In  bed,  flexing,  extending,  abducting  and  adducting  the  legs 
separately  and  together  are  practised.  The  attempt  to  place  the 
heel  of  one  foot  on  the  great  toe  of  the  other  and  on  the  knee  and 
permit  it  to  travel  slowly  along  the  shin  to  the  ankle  is  made.  These 
exercises  are  attempted  alternately  with  each  leg  both  with  open 
and  closed  eyes,  and  are  performed  many  times  with  frequent  rests 
and  encouragement. 

The  exercises  performed  out  of  bed  consist  of  slowly  seating  in 
a  chair  and  slowly  rising  with  the  heels  close  together  and  without 
the  use  of  a  cane,  careful  walking,  stepping,  placing  of  the  feet, 
standing  with  the  feet  together,  various  movements  of  the  arms, 
walking  along  a  painted  line  on  the  floor,  etc.  The  exercises  must 
be  progressively  attempted  and  great  perseverence  is  necessary. 
Fatigue,  however,  must  be  avoided. 

In  the  terminal  stages  decubitus  should  be  prevented  or,  if  it 
develops,  should  be  treated  as  in  paresis. 

Syphilitic  neuralgia  rarely  needs  any  treatment  but  specifics, 
although  analgesics  may  be  necessary.  The  treatment  of  syphilitic 
neuritis  and  polyneuritis  after  the  use  of  specific  medication  consists 
of  the  use  of  massage  and  electricity. 

Standard  Treatment. — All  cases  showing  syphilitic  involvement 
of  the  cerebrospinal  axis  by  examination  of  the  spinal  fiuid  should 

1  The  Treatment  of  Tabetic  Ataxia,  Philadelphia,  1902. 


STANDARD  TREATMENT  355 

receive  intraspinal  injections  as  well  as  other  vigorous  specific 
treatment.  The  author  usually  uses  the  Ogilvie  and  Byrnes  methods 
alternately  at  intervals  of  7  to  10  days,  in  order  to  bring  both  specifics 
into  contact  with  the  treponemata.  The  Wile  method  certainly 
promises  much  on  account  of  its  simplicity  and  in  all  probability 
in  the  future  will  be  the  method  of  choice  for  the  intraspinal 
administration  of  salvarsan. 

The  intraspinal  treatments  should  be  continued  until  the  spinal 
fluid  becomes  negative,  or  in  the  case  of  paretics,  for  eight  or  ten 
injections  if  no  objective  or  subjective  improvement  is  noted.  If 
intraspinal  treatments  do  not  relieve  cerebral  symptoms,  intra- 
cranial, either  subdural  or  intraventricular,  injections  should  be 
given  a  trial.  No  case  of  syphilis,  from  the  chancre  to  paresis, 
should  be  given  up  until  all  means  of  treatment  are  exhausted. 

The  standard  for  cure  of  a  case  of  syphilis  showing  central  nervous 
system  involvement  consists  of  a  constantly  negative  spinal  fluid 
as  well  as  a  negative  blood  Wassermann  without  any  increase  in 
symptoms  for  a  period  of  at  least  two  years  following  the  last 
treatment. 


CHAPTER  XIX. 
SYPHILIS  OF  THE  EYE  AND  EAR. 

THE   EYE. 

Pathology. — Eyelid. — Chancre  of  the  eyelid  has  been  discussed 
in  Part  I  in  the  chapter  on  CUnical  History.  Nearly  any  of  the 
syphilodermata  may  occur  in  this  locality.  Papular  lesions  have 
been  observed  on  the  palpebral  conjunctivae.  Gummata  of  the 
eyelids  are  of  not  infrequent  occurrence  but  present  no  unusual 
features. 

Iris. — Syphilitic  iritis  is  quite  often  seen,  being  the  most  common 
of  all  luetic  conditions  of  the  eye.  The  process  is  generally  plastic 
in  type,  the  iris  being  congested,  thickened  and  of  a  grayish  color. 
There  is  more  or  less  injection  of  the  anterior  ciliary  vessels  and  the 
anterior  chamber  contains  a  plastic  exudate.  Serous  iritis  is  also 
sometimes  noted,  in  which  an  exudate  consisting  of  grayish  spots 
on  the  lower  half  of  Descemet's  membrane  is  seen.  In  this  type  the 
ciliary  injection  is  not  so  great.  Synechia  more  frequently  follows 
the  plastic  type  than  the  serous  type. 

Papules  of  the  iris  which  correspond  to  the  papular  syphiloderm 
are  sometimes  seen  on  its  pupilary  border  or  on  its  anterior  surface. 
They  are  usually  single  and  about  one  millimeter  in  diameter,  but 
may  be  multiple.  The  color  varies  from  a  reddish  brown  to  a  yellow. 
Gummata  of  the  iris  are  of  exceedingly  rare  occurrence.  When  found 
they  vary  from  two  to  six  millimeters  in  diameter  and  present  no 
peculiarities  not  observed  in  gummata  of  other  localities. 

Treponemata  have  been  found  in  the  aqueous  in  acute  iritis. 

Ciliary  Body. — Cyclitis  is  usually  associated  with  iritis  but 
may  be  observed  alone.  As  with  iritis  it  may  be  of  plastic  or  serous 
type  or  gummata  may  originate  in  the  ciliary  body  or  involve  it  by 
extension  from  the  iris. 

Cornea. — Syphilitic  involvement  of  the  cornea  is  rare  in  the 
acquired  form  of  the  disease  but  may  occur  as  diffuse  parenchyma- 
tous or  interstitial  keratitis  in  which  there  is  a  cloiidy  opacity  in  the 
deeper  layers  of  the  cornea,  as  keratitis  punctata,  characterized  by 
the  deposit  of  grayish  spots  about  one  millimeter  in  diameter  in 
the  corneal  parenchyma,  or  as  gummatous  infiltration. 

Sclera. — Syphilis  may  involve  the  sclera  as  a  diffuse  infiltra- 
tion or  as  circumscribed  gummata.    In  the  former  there  is  thinning 


PLATE  V 


Syphilitic  Retinitis.     (Norris  and  Oliver.) 


THE  EYE 


357 


of  the  affected  area  while  in  the  latter  there  is  thickening.     The 
process  may  be  complicated  by  iritis  or  cyclitis. 

Choroid. — ^The  choroid  is  rarely  alone  the  seat  of  syphilis,  as 
its  involvement  usually  is  observed  as  an  extension  from  the  ciliary 
body  or  in  connection  with  retinitis.  Syphilitic  choroiditis  is,  how- 
ever, next  to  iritis,  the  most  frequent  luetic  affection  of  the  eye. 
As  usually  observed  there  are  at  first  yellowish  patches  of  exudate 
scattered  over  the  choroid.  Later  they  may  become  white,  due  to 
atrophy  of  the  choroid  and  be  surrounded  by  a  zone  of  pigment. 
Gummata  of  the  choroid  have  been  described  but  are  exceedingly 
rare. 


Fig.  72. — Syphilitic  iritis  and  keratitis. 


Retina. — Retinitis  of  syphilitic  origin  may  occur  alone  but  is 
usually  an  extension  from  disease  of  the  choroid.  Several  types 
are  observed:  First,  a  simple  retinitis  which  is  an  inflammation  of 
the  superficial  layers  of  the  retina  and  in  which  there  is  hj^eremia 
of  serous  type  and  edema;  second,  an  exudative  retinitis,  showing 
more  or  less  deposit  of  yellowish  exudate  scattered  over  the  retina; 
third,  hemorrhagic  retinitis,  due  to  endarteritis  and  the  formation  of 
thrombi;  and  fourth,  the  so-called  central  recurring  retinitis  of 
von  Graefe.  The  latter  type  is  exceedingly  rare  and  is  characterized 
by  the  appearence  of  small,  white  punctate  dots  in  the  macula. 

Optic  Nerve.- — The  optic  nerve  may  be  the  seat  of  the  syphilitic 
process  in  its  intra-orbital  end  as  well  as  in  its  intracranial  or 
intracerebral  portion.    Papillitis  or  inflammation  of  the  intra-orbital 


358  SYPHILIS  OF  THE  EYE  AND  EAR 

end  of  the  optic  nerve  is  characterized  by  marked  swelHng  of  the 
optic  disk,  more  or  less  edema  and  cellular  infiltration. 

Lacrimal  Apparatus.— Syphilis  of  the  lacrimal  apparatus  is 
usually  due  to  an  extension  from  adjacent  structures  but  cases 
have  been  reported  in  which  gummata  were  first  observed  in  the 
lacrimal  gland. 

Orbit. — ^The  bones  of  the  orbit  may  be  the  seat  of  the  syphilitic 
process,  but  the  pathological  picture  does  not  differ  from  that 
observed  in  other  bones. 

Clinical  History. — Eyelid. — Chancre  of  the  eyelid  as  well  as  the 
various  syphUodermata  and  syphilomycodermata  present  no  features 
which  are  not  found  in  these  lesions  in  other  localities.  There  will, 
however,  be  more  or  less  deformity,  depending  upon  the  extent  of 
the  pathological  process. 

Iris. — Syphilitic  iritis  is  the  most  common  of  all  luetic  conditions 
of  the  eye.  It  usually  occurs  during  the  first  year  of  the  disease 
and  may  be  present  before  the  chancre  has  healed  but  sometimes 
is  observed  considerably  later.  There  is  nothing  in  the  symptoma- 
tology pathognomonic  of  syphilis,  as  the  same  condition  may  be 
found  in  non-luetic  iritis.  It  is  characterized  by  marked  ciliary 
injection,  the  vessels  forming  a  zone  around  the  corneal  margin 
with  more  or  less  conjunctival  congesaon,  swelling  of  the  iris, 
contraction,  irregularity  and  sluggishness  of  the  pupil  due  to  pos- 
terior synechia,  turbidity  of  the  aqueous,  occasional  increased  ten- 
sion of  the  eyeball,  lacrimation,  photophobia,  interference  with 
vision  and  pain.  The  latter  symptom  is  usually  not  so  severe  as 
in  non-luetic  iritis. 

The  serous  type  of  syphilitic  iritis  is  less  frequently  observed 
than  the  plastic  type,  the  symptoms  are  less  marked  and  the  con- 
dition shows  more  tendency  to  become  chronic.  The  serous  type 
is  also  more  frequently  complicated  by  cyclitis  or  choroiditis. 

Gummatous  iritis,  which  is  an  exceedingly  rare  condition,  and 
occurs,  as  a  rule,  late  in  the  course  of  syphilis,  presents  a  clinical 
picture  similar  to  that  just  described,  with  the  addition  of  one  or 
more  gummata  observed  as  distinct  tumors  varying  in  size  from 
two  to  six  millimeters  in  diameter  and  situated  in  or  on  the 
iris. 

Ciliary  Body. — While  the  ciliary  body  is  occasionally  alone  the 
seat  of  the  syphilitic  process,  it  usually  is  affected  with  the  iris  or 
choroid.  The  symptoms  consist  of  tenderness  in  the  ciliary  region, 
deposits  on  Descemet's  membrane,  increased  tension  in  the  serous 
type  and  diminished  in  the  plastic. 

Gummata  when  arising  in  the  ciliary  body  usually  extend  to  the 
choroid.  The  intra-ocular  tension  is  usually  diminished,  sometimes 
markedly  so. 


THE  EYE  359 

Cornea. — Syphilis  of  the  cornea  in  the  acquired  form  is  a  rare 
condition  and  is  almost  always  observed  late  in  the  course  of  the 
disease. 

Diffuse  pare7ichymatous  or  interstitial  keratitis  may  begin  either 
in  the  centre  or  at  the  margin  and  consists  of  a  grayish  opacity  which 
soon  spreads  and  involves  the  entire  cornea,  obscuring  the  iris. 
Deep-seated  bloodvessels  soon  pervade  more  or  less  of  the  cornea, 
causing  a  yellowish-red  discoloration.  In  uncomplicated  cases 
the  subjective  symptoms  of  photophobia,  lacrimation,  pain  and 
interference  with  vision  are  dependent  upon  the  severity  of  the 
process,  but  are  usually  mild  in  character.  The  condition  is, 
however,  usually  complicated  by  iritis,  choroiditis,  cyclitis  and 
changes  in  the  vitreous  with  the  accompanying  symptoms. 

Keratitis  inm.ctata  characterized  by  the  deposit  of  small  grayish 
spots  in  the  corneal  parenchyma  produces  no  other  symptom, 
there  being  no  injection  and  the  remainder  of  the  cornea  appearing 
normal. 

Gummata  of  the  cornea  is  a  most  rare  condition  and  will  give 
rise  to  symptoms  depending  upon  the  extent  of  the  process. 

Sclera. — Syphilis  involving  only  the  sclera  is  rare.  The  diffuse 
infiltration  sometimes  observed  will  cause  a  deep  bluish-red  injec- 
tion of  the  affected  portion.  It  appears  like  a  blotch  of  color  rather 
than  injected  vessels.  There  is  also  usually  conjunctival  injection. 
More  or  less  thinning  with  consequent  bulging  of  the  eyeball  is 
observed.  The  process  is  usually  bilateral  and  partial  or  complete 
blindness  will  result,  depending  upon  the  severity  of  the  process. 
The  subjective  symptoms  vary  with  the  condition  and  consist  of 
pain,  usually  of  a  dull,  aching  character,  but  sometimes  boring, 
lacrimation  and  photophobia. 

Gummata  of  the  sclera  are  exceedingly  rare  and  vary  in  size 
from  one  or  two  millimeters  to  two  or  three  centimeters  in  diameter. 
The  larger  gummata  usually  involve  the  ciliary  body.  They  are 
generally  hard  and  sensitive,  while  the  conjunctival  injection  is 
marked.  Subjectively  there  is  more  or  less  pain,  photophobia  and 
some  interference  with  the  mobility  of  the  eyeball. 

Choroid. —  Diffuse  syphilitic  choroiditis  is  usually  associated 
with  retinitis  and  occurs,  as  a  rule,  early  in  the  course  of  the  disease, 
generally  during  the  first  year.  No  external  signs  of  the  condition 
exist  but  the  ophthalmoscope  reveals  at  first  yellowish  patches  of 
exudate  scattered  over  the  choroid,  especially  in  the  region  of  the 
macula,  while  the  retinal  vessels  are  seen  to  pass  over  them.  Later 
there  is  absorption  of  exudate  and  atrophy  of  the  choroid  occurs  in 
patches.  These  appear  as  white,  irregularly  shaped  areas,  the 
sclera  showing  through,  and  often  marked  with  choroidal  vessels, 
and  more  or  less  pigment. 


360  SYPHILIS  OF   THE  EYE  AND  EAR 

The  subjective  symptoms  are  disturbances  of  vision,  consisting 
of  diminution  of  acuteness,  the  appearance  of  spots,  the  distortion 
of  objects  and  flashes  of  Ught  before  the  eyes.  Pain  is  absent  in 
this  condition.  Gummata  of  the  choroid  is  an  exceedingly  rare 
condition  and  is  usually  not  recognized  during  life. 

Retina. — Syphilitic  retinitis  is  quite  common  and  usually  occurs 
in  association  with  choroiditis  and  often  with  iritis.  It  is  generally 
found  during  the  first  or  second  years  of  the  disease,  but  may  occur 
later.  Both  eyes  are  usually  involved  but  sometimes  only  one  is 
affected.  No  external  objective  symptoms  are  found.  In  the  simple 
form  the  ophthalmoscope  reveals  a  hazy  condition  of  the  fundus, 
most  marked  around  the  disk,  the  margins  of  which  are  more  or 
less  indistinct.  The  veins  are  tortuous  and  dilated,  while' the  vessels 
are  hidden  in  places  by  the  edema.  Occasionahy  hemorrhages  are 
seen.  There  is  impairment  of  vision,  contraction  of  the  visual 
field,  distorted  vision  and  scotomata. 

In  the  exudative  type  of  retinitis  the  fundus  is  indistinct,  due, 
not  only  to  swelling  of  the  retina  and  disk,  but  also  to  fine  dust- 
like opacities  in  the  posterior  portion  of  the  vitreous  which  cause 
the  disk  to  appear  red  and  hazy.  Scattered  over  the  fundus,  espe- 
cially in  the  region  of  the  macula  are  seen  grayish  or  white  spots 
sometimes  surrounded  by  pigment.  There  is  diminution  in  the 
acuteness  of  vision,  depending  upon  the  severity  of  the  process, 
night-blindness,  flashes  of  light,  distortion  of  vision,  scotomata 
and  contraction  of  the  visual  field. 

In  hemorrhagic  retinitis  there  is  added  to  the  signs  and  symptoms 
just  mentioned  numerous  hemorrhages  which  may  be  superficial 
and  appear  flame-shaped  or  deep  and  roundly  irregular. 

The  central  recurring  retinitis  of  von  Graefe,^  which  is  very  rare, 
is  at  first  characterized  by  small,  white,  punctate  dots  grouped  in 
the  macula,  as  well  as  by  an  opacity  in  the  vicinity  of  the  latter. 
There  also  is  more  or  less  disturbance  of  vision.  The  condition 
develops  suddenly,  lasts  a  few  days  and  disappears  but  recurs  in 
a  few  weeks.  In  subsequent  attacks  to  the  appearance  of  the 
punctate  spots  in  the  macula  are  added  irregular  white  streaks 
radiating  from  the  optic  disk  into  the  retina,  generafly  along  the 
vessels,  which  may  be  elevated.  Punctate  spots  are  also  scattered 
over  the  entire  fundus. 

Optic  Nerve. — Syphilitic  papillitis  is  characterized  by  swelling 
of  the  disk,  which  is  of  a  whitish  or  grayish  color,  is  striated  and 
often  contains  spots  and  hemorrhages.  The  margins  are  indis- 
tinguishable and  the  disk  is  only  located  by  the  convergence  of  the 
bloodvessels.    The  arteries  are  usually  thin  but  may  be  of  normal 

1  Arch.  f.  Ophth.,  1860,  vii,  p.  211. 


THE  EYE  361 

size,  while  the  veins  are  distended  and  tortuous.  The  retina  sur- 
rounding the  disk  is  edematous,  congested  and  white  spots  and 
hemorrhages  are  seen  in  it.  There  is  more  or  less  disturbance  of 
vision,  sometimes  amounting  to  complete  blindness,  although  often 
there  is  less  disturbance  than  would  be  expected  from  the  ophthal- 
moscopic picture.    There  may  be  hemianopsia  or  scotomata. 

Lacrimal  Apparatus. — Gummata  of  the  lacrimal  gland  have 
been  described  and  cause  symptoms  depending  upon  the  size  of 
the  gumma. 

Dacryocystitis  not  infrequently  occurs,  usually  as  an  extension 
from  other  parts  and  causes  an  epiphora,  and  a  sense  of  fulness  in 
the  region  of  the  lacrimal  sac. 

Orbit. — The  bones  of  the  orbit  are  rather  rarely  affected  by 
syphilis  and  the  symptoms  will  depend  upon  the  extent  and  severity 
of  the  process.  There  is  usually  more  or  less  pain  and  swelling  and 
when  a  gumma  is  deeply  situated  in  the  orbit  or  is  very  large  there 
will  be  exophthalmus,  and  marked  fixity  of  the  eyeball. 

Diagnosis. — Eyelid. — Chancre  of  the  eyelid  as  well  as  the  various 
syphilodermata  and  syphilomycodermata  are  to  be  diagnosed  upon 
the  same  grounds  as  these  lesions  of  other  localities. 

Iris. — Syphilis  is  the  most  frequent  etiological  factor  in  iritis, 
so  should  be  thought  of  in  all  cases.  There  is  nothing  in  the  clinical 
picture,  however,  which  will  differentiate  it  from  iritis  due  to  other 
causes  except,  perhaps,  that  the  pain  is  not  so  pronounced  as  in 
some  other  forms.  The  diagnosis  therefore  must  rest  upon  the  his- 
tory, the  finding  of  other  evidences  of  syphilis  (syphilodermata  are 
usually  present),  positive  laboratory  tests  and  therapeutic  measures. 

Ciliary  Body. — Syphilis  of  the  ciliary  body  is,  as  a  rule,  asso- 
ciated with  syphilis  of  the  iris  or  choroid,  and  its  diagnosis  will 
depend  upon  the  same  factors  as  the  diagnosis  of  syphilis  of  those 
portions  of  the  eye. 

Cornea. — Syphilitic  keratitis  is  rare  in  the  acquired  form  of  the 
disease  but  syphilis  is  the  most  frequent  etiological  factor  in  inflam- 
mation of  the  cornea.  It  is,  as  a  rule,  complicated  by  iritis,  choroid- 
itis, and  cyclitis  and  its  diagnosis  will  depend  upon  the  indirect 
evidence  of  history,  laboratory  findings,  etc. 

Sclera. — Syphilis  of  the  sclera  is  also  to  be  diagnosed  by  the 
history,  presence  of  other  manifestations  of  syphilis,  positive  Was- 
sermann  or  luetin  tests,  and  improvement  under  antisyphilitic 
treatment.  Gumma  of  the  sclera,  although  exceedingly  rare,  must 
be  differentiated  from  malignant  growth  and,  as  a  rule,  may  be 
accomplished  by  the  above  factors.  Tumors  of  the  sclera  occurring 
in  the  young  would  be  against  it  being  malignant. 

Choroid. — Syphilis  is  the  cause  of  the  majority  of  cases  of 
choroiditis,  so  should  always  be  thought  of  in  all  such  cases.    The 


362  SYPHILIS  OF  THE  EYE  AND  EAR 

ophthalmoscopic  picture  is  usually  quite  characteristic,  but  a  diag- 
nosis of  syphilis  of  the  choroid  should  rarely  be  made  without 
corroborative  evidence. 

Retina. — Syphilitic  retinitis,  as  a  rule,  presents  an  ophthalmo- 
scopic picture  which  is  scarcely  to  be  mistaken  for  retinitis  of  other 
etiology,  however,  the  findings  in  the  eye-ground  should  be  substan- 
tiated by  the  exclusion  of  other  types  of  retinitis,  such  as  albumin- 
uric and  diabetic  by  the  examination  of  the  urine,  by  the  history, 
the  presence  of  other  manifestations  of  syphilis,  positive  laboratory 
findings  and  in  some  cases  the  improvement  of  the  condition  under 
specific  therapy. 

Optic  Nerve. — There  is  nothing  pathognomonic,  either  in  the 
symptomatology  or  the  ophthalmoscopic  picture  of  syphilitic  papil- 
litis, so  its  differentiation  from  papillitis  due  to  other  etiology  must 
be  accomplished  by  the  diagnosis  of  the  presence  of  syphilis  in  other 
portions  of  the  body  and  perhaps  by  its  improvement  upon  the 
administration  of  specific  treatment. 

Lacrimal  Apparatus. — Syphilis  of  the  lacrimal  apparatus,  also, 
is  not  characteristic  and  its  diagnosis  can  only  be  accomplished 
by  indirect  evidence. 

Orbit. — Syphilitic  disease  of  the  orbit  is  to  be  differentiated 
from  tumors  of  various  types  and  the  presence  of  foreign  bodies, 
and  as  with  syphilis  of  the  lacrimal  apparatus,  is  only  to  be  accom- 
plished by  indirect  evidence. 

Prognosis. — Iris. — The  prognosis  of  the  curing  of  syphilitic  iritis 
is  good  but  often  the  sequelae  are  most  troublesome.  In  the  milder 
cases,  if  posterior  synechiae  are  formed,  they  may  be  broken  down 
with  atropine  so  that  pupillary  activity  may  be  restored,  although 
uveal  pigment  will,  as  a  rule,  be  found  on  the  anterior  lens  capsule. 
Sometimes  when  the  process  has  been  severe  synechise  are  formed 
which  cannot  be  overcome  with  atropine  and  permanent  distor- 
tion of  the  pupil  is  seen.  However,  if  the  pupil  is  not  so  fixed  that 
communication  between  the  anterior  and  posterior  chambers  is 
closed,  some  sight  will  remain,  although  it  will  be  more  or  less 
damaged.  If  the  iris  is  so  fixed  that  the  communication  is  com- 
pletely closed,  secondary  glaucoma  will  develop  with  a  bulging 
bombe  iris,  and,  as  a  rule,  blindness  will  result. 

Ciliary  Body. — The  prognosis  of  syphilitic  cyclitis  when  exist- 
ing alone  is  good  if  recognized  early  and  treatment  is  vigorously 
applied,  although  glaucoma  may  result.  However,  as  cyclitis  is 
usually  associated  with  iritis  or  choroiditis  the  outcome  will  depend 
upon  the  outcome  of  the  associated  condition. 

Cornea. — Syphilitic  keratitis  is,  as  a  rule,  very  amenable  to  treat- 
ment, and  even  in  the  most  severe  cases  the  opacity  of  the  cornea 
may  clear  in  a  remackable  manner,  so  that  only  the  most  careful 


THE  EYE  363 

examination  will  reveal  the  fact  that  it  has  been  affected.  This 
is  not  always  the  case,  however,  and  more  or  less  permanent  opacity 
is  often  left.  The  prognosis  as  to  sight  must  be  guarded  until  the 
cornea  has  sufficiently  cleared  for  an  ophthalmoscopic  examination 
to  reveal  the  presence  or  absence  of  a  choroiditis. 

Sclera. — The  prognosis  of  syphilis  of  the  sclera  will  depend  upon 
the  severity  of  the  process,  the  mild  cases  recovering  without  serious 
permanent  damage,  the  severe  ones  leaving  more  or  less  blindness. 

Choroid. — The  prognosis  of  syphilitic  choroiditis  is  always 
grave,  although  if  the  macula  escapes  some  vision  may  remain. 

Retina. — Syphilitic  retinitis  must  be  considered  a  serious  con- 
dition, yet  if  recognized  early  and  antisyphilitic  treatment  vigor- 
ously pushed,  the  prognosis  is  fair,  although  at  best  there  is  usually 
some  impairment  of  the  vision.  If  neglected,  syphilitic  retinitis 
is  often  followed  by  disseminated  choroiditis,  pigmentary  degenera- 
tion of  the  retina  and  optic  atrophy. 

Optic  Nerve. — The  prognosis  of  syphilitic  papillitis  is  bad, 
for  although  under  specific  treatment  the  process  may  subside,  more 
or  less  permanent  damage  is  left.  Most  severe  cases  develop  optic 
atrophy,  either  partial  or  complete  and  the  process  may  extend  to 
the  brain  with  even  fatal  consequences. 

Lacrimal  Apparatus. — Syphilitic  involvement  of  the  lacrimal 
apparatus,  if  recognized  early  and  vigorously  treated,  is  usually 
followed  by  complete  recovery. 

Orbit. — The  prognosis  of  syphilitic  disease  of  the  orbit  will 
depend  upon  the  extent  and  severity  of  the  process. 

Treatment. — All  syphilitic  involvement  of  the  eye  requires 
thorough  and  persistent  specific  medication  as  well  as  the  general 
treatment  outlined  in  Part  I.  Added  to  these  most  conditions 
should  receive  local  treatment. 

Iris. — Atropine  (1  per  cent,  solution)  should  be  administered 
as  soon  as  the  diagnosis  is  reached.  This  drug  causes  mydriasis, 
puts  the  iris  at  rest,  prevents  the  formation  of  adhesions  and  tends 
to  break  up  those  already  formed.  The  atropine  should  be  instilled 
every  two  hours  at  first  until  the  pupil  is  dilated,  then  three  or  four 
times  a  day  for  a  week  or  ten  days  after  all  injection  has  left. 

For  the  pain  hot  compresses  are  very  beneficial.  Leeches  applied 
to  the  temple  near  the  outer  canthus  act  not  only  in  relieving  pain 
but  in  reducing  the  injection.  The  removal  of  25  to  30  c.c.  of  blood 
with  an  artificial  leech  may  readily  be  accomplished.  The  eye 
should  be  protected  from  light  and  in  the  beginning,  at  least,  the 
patient  should  be  placed  in  bed. 

Cornea. — In  syphilitic  keratitis  it  is  also  important  to  keep  the 
pupil  dilated  with  atropine  throughout  the  course  of  the  disease. 
The  eye  should  be  bathed  with  boric  acid  solution  and  protected 


364  SYPHILIS  OF   THE  EYE  AND  EAR 

from  the  light  by  a  shade  or  smoked  glasses.  When  the  opacity 
begins  to  clear  an  ointment  such  as  yellow  oxide  of  mercury  and 
calomel  should  be  applied. 

Sclera. — As  stated  in  the  section  on  Clinical  History,  syphilis 
involving  only  the  sclera  is  rare,  therefore  its  treatment  consists 
of  treating  the  complicating  conditions.  The  eye  should  obtain 
complete  rest  and  hot  bathing  and  atropine  applied. 

Choroid  and  Retina. — Syphilitic  disease  of  the  choroid  and 
retina  usually  are  associated,  and  even  when  occurring  alone  the 
treatment  is  the  same.  In  no  other  condition  is  vigorous  and 
prompt  antisyphilitic  treatment  more  desirable.  Atropine  should 
be  used  locally  and  smoked  glasses  worn. 

Optic  Nerve. — Papillitis  requires  no  other  treatment  than 
specific  and  general  measures,  except  the  use  of  smoked  glasses. 

Numerous  workers  have  proposed  the  direct  installation  of  anti- 
syphilitic  remedies  in  the  conjuctival  sac  in  the  various  syphilitic 
diseases  of  the  eye.  Most  of  these  measures  have  met  with  com- 
paratively little  success.  Lamb^  has  advocated  the  use  of  salvar- 
sanized  serum  prepared  after  the  method  of  Swift  and  Ellis^  for 
intraspinal  medication.  It  is  kept  on  ice  in  sealed  ampules  of  1  c.c. 
capacity  and  warmed  to  body  temperature  before  using.  Numerous 
types  of  cases  have  been  treated,  interstitial  keratitis,  iritis,  gum- 
matous iritis,  iridocyclitis,  chorioretinitis  and  even  optic  atrophy. 
Lamb  states  that  the  results  sometimes  were  so  rapid  as  to  be  almost, 
startling.  The  author  has  employed  this  method  of  treatment  in 
syphilitic  iritis  with  very  satisfactory  results. 

Lacrimal  Apparatus. — Dacryocystitis  if  seen  early  enough 
usually  will  clear  up  under  specific  medication,  or  at  least  with  the 
installation  of  bichloride  solution  (1  to  5000)  into  the  coujuctival 
sac.  If  it  does  not,  surgical  procedures  may  be  necessary.  The 
canaliculi  should  be  opened  and  the  lacrimal  sac  washed  out 
with  antiseptic  and  astringent  solutions.  If,  in  spite  of  this  treat- 
ment, the  process  persists  the  lacrimal  sac  should  be  removed, 
and  the  cavity  irrigated  with  antiseptic  solutions  until  granulation 
occurs. 

THE   EAR. 

Pathology. — Chancres  of  the  auricle  have  been  recorded,  but  as 
with  those  of  the  great  toe  and  nose  mentioned  in  Part  I,  are  merely 
medical  curiosities. 

Syphilodermata  of  the  auricle  and  external  auditory  meatus 
are  of  comparatively  frequent  occurrence,  condylomata  being  most 
often  seen,  while  gummata  have  been  reported. 

1  Washington,  Med.  Ann.,  1915,  xiv,  p.  69. 

2  New  York  Med.  Jour.,  1912,  xcvi,  p.  53. 


THE  EAR  365 

The  middle  ear  may  be  the  seat  of  the  syphiUtic  process  early  m 
the  course  of  the  disease  when  the  infection  may  extend  from  the 
nasopharynx  through  the  Eustachian  tube.  Endarteritis  of  the 
mucous  membrane  and  periostitis  of  the  bony  walls,  as  well  as 
gummata  are  sometimes  noted.  In  syphilitic  involvement  of  the 
internal  ear  the  pathological  process  consists  of  hyperplasia  of 
connective  tissue,  especially  of  the  periosteum  and  infiltration  of 
small  round  cells.  A  serous  labyrinthitis  following  a  severe  hyper- 
emia may  occur  and  pus  may  be  formed.  Endarteritis  and  hemor- 
rhage into  the  cochlear  nerve  may  occur,  while  gummata  of  the 
petrous  portion  of  the  temporal  bone  have  been  observed. 

Clinical  History. — The  chancres  and  syphilodermata  found  on 
the  auricle  and  in  the  external  auditory  meatus  present  no  features 
in  themselves  which  are  essentially  different  from  these  lesions  in 
other  localities.  Condylomata  of  the  external  auditory  meatus  will 
produce  a  watery,  offensive  discharge  and  the  swelling  may  com- 
pletely occlude  the  canal.  More  or  less  deafness  will  result  and 
tinnitus  is  sometimes  observed. 

When  the  middle  ear  is  involved  in  the  syphilitic  process  there 
will  be  more  or  less  pain,  which  is  worse  at  night,  although  at  no 
time  is  it  very  severe,  air  conduction  of  sound  is  impaired,  while 
bone  conduction  is  normal  and  the  membrani  tympani  shows 
evidence  of  exudate  without  congestion. 

Syphilitic  involvement  of  the  inner  ear  may  occur  very  early  in 
the  course  of  the  disease,  according  to  Stein^  as  early  as  one  week 
following  the  appearance  of  the  chancre.  The  usual  time  of  its 
appearance,  however,  is  between  the  sixth  and  twelfth  months, 
but  it  may  occur  years  later. 

The  onset  of  the  condition  is'  sudden  and  deafness  develops 
rapidly,  occasionally  during  one  night.  Usually  the  deafness  is 
absolute,  that  is,  the  hearing  of  all  tones  is  lost,  but  sometimes  the 
higher  tones  are  not  heard,  while  the  lower  ones  are.  The  condition 
is  usually  bilateral  but  is  sometimes  seen  first  in  one  ear,  the  other 
being  affected  soon  after.  Bone  conduction  is  diminished  from  the 
beginning.  There  is  usually  tinnitus,  the  noises  seeming  to  be  high, 
such  as  ringing  of  small  bells.  Vertigo  js  frequent  and  sometimes  pain 
deep  in  the  ear  is  felt. 

Menier's  syndrome  is  occasionally  seen  in  syphilitic  involvement 
of  the  internal  ear. 

Diagnosis. — ^The  diagnosis  of  chancre  and  syphilodermata  on  the 
auricle  and  in  the  external  auditory  meatus  will  depend  upon  the 
same  factors  as  the  diagnosis  of  these  lesions  of  other  localities. 

There  is  nothing  in  the  clinical  picture  of  syphilis  of  the  middle 

1  Annals  of  Otology,  Rhinology  and  Laryngology,  1914,  xxiii,  p.  116. 


366  SYPHILIS  OF  THE  EYE  AND  EAR 

ear  to  distinguish  it  from  middle-ear  involvement  of  other  causes, 
except,  perhaps,  the  usual  increase  of  the  pain  at  night.  The  diag- 
nosis must  depend  upon  the  history,  the  presence  of  other  syphilitic 
lesions  or  symptoms,  positive  laboratory  tests  and  the  response  to 
antisyphilitic  treatment. 

The  same  may  be  said  concerning  syphilis  of  the  inner  ear  except, 
perhaps,  in  the  case  of  Menier's  syndrome  due  to  syphilis  which, 
according  to  Grey^  as  stated  by  Stein,  is  characterized  by  but  one 
attack,  while  if  due  to  other  causes  there  is  likelihood  of  similar 
attacks. 

Prognosis. — The  prognosis  of  chancre  and  the  syphilodermata  of 
the  auricle  and  external  auditory  meatus  differs  in  no  respect  from 
the  prognosis  of  these  lesions  elsewhere. 

Syphilis  of  the  middle  and  inner  ear  is  more  serious  and  partial 
or  complete  permanent  deafness  will  result,  depending  upon  the 
extent  of  the  process,  the  time  it  is  recognized  and  the  treatment 
instituted. 

Treatment. — The  treatment  of  chancre  and  the  syphilodermata 
of  the  auricle  and  external  auditory  meatus  is  the  same  as  the  treat- 
ment of  these  lesions  elsewhere. 

Syphilis  of  the  middle  and  internal  ear  is  to  be  treated  solely 
by  specifics  and  general  measures,  as  loc«,l  treatment  is  of  no  avail. 
The  injection  of  pilocarpine  has  been  recommended  in  these  con- 
ditions but  is  of  little  or  no  value. 


PART  III. 

CHAPTER  XX. 
CONGENITAL  SYPHILIS. 

NOMENCLATURE. 

Considerable  uncertainty  seems  to  exist  in  regard  to  the  use  of 
the  terms  congenital  and  hereditary  syphihs.  Sturgis^  states  that 
hereditary  syphihs  may  be  divided  into  two  varieties,  congenital 
and  hereditary,  the  difference  being  that  in  congenital  syphilis  the 
symptoms  are  present  at  birth  and  in  hereditary  syphilis  they 
appear  at  a  longer  or  shorter  time  after  birth. 

Marshall  states  that  congenital  syphilis  embraces  all  cases 
which  show  signs  of  syphilis  at  or  soon  after  birth  and  that  both 
cases  infected  during  pregnancy  and  post-conceptional  cases  are 
included,  and  that  hereditary  syphilis  applies  to  cases  of  infection 
of  the  ovum  by  maternal  syphilis  or  of  the  ovum  by  spermatozoa 
of  the  father. 

StilP  holds  the  same  views  as  Marshall  but  states  that  while  the 
differences  mentioned  exist  it  is  inexpedient  to  use  the  different 
terms,  as  there  is  no  clear  evidence  of  any  corresponding  difference 
of  course.  This  writer  also  suggests  that  the  term  "infantile 
syphilis"  might  be  used  to  include  also  those  cases  of  infection  of 
the  child  during  birth  from  lesions  on  the  maternal  genitals  and 
those  infected  soon  after  birth  by  kissing,  etc. 

It  seems  to  the  author  that  the  term  hereditary  syphilis  should 
be  applied  to  all  cases  of  syphilis  developing  in  utero,  and  the  term 
congenital  syphilis  should  include  all  such  cases  as  well  as  those 
contracted  by  the  child  during  its  passage  through  the  birth  canal. 

HISTORICAL. 

As  pointed  out  in  Part  I,  Buret  affirms  that  hereditary  syphilis 
was  known  to  the  Chinese  centuries  ago.    This  same  writer^  states 

1  Morrow:  System  of  Genito-urinary  Diseases,  Syphilology,  and  Dermatology, 
New  York,  1898,  p.  603. 

2  Syphilology  and  Venereal  Disease,  New  York,  1906,  p.  317. 

3  System  of  Syphilis,  London,  1908,  i,  p.  284. 

■i  Buret:  Syphilis  in  the  Middle  Ages  and  in  Modern  Times,  American  edition, 
Philadelphia,  1895,  p.  210. 


368  CONGENITAL  SYPHILIS 

that  Almenar,  in  1502,  and  Bethencourt,  in  1526,  considered  "  syphilis 
incurable,  was  inevitably  transmitted  to  children  and  could  even 
in  these  latter  not  show  itself  until  adult  life." 

Paracelsus,^  in  1529,  stated  that  it  was  an  hereditary  disease  and 
could  be  transmitted  from  father  to  child  "Fit  morbus  hereditarius, 
et  transit  a  patre  ad  filium." 

Most  other  writers  following  Paracelsus  did  not  recognize  this 
manner  of  infection  until  Fallopius^  wrote,  in  1555,  "You  will  see 
SDiall  children  born  of  infected  women  who  suffer  for  the  sins  of 
their  parents,  and  who  are  born  in  a  simicooked  condition." 

Rondelet,^  in  1689,  wrote  of  syphilitic  infection  of  children  from 
nurses,  but  hinted  only  obscurely  that  syphilis  in  the  parents  might 
be  responsible  for  "certain  transmitted  diseases  in  the  children." 

Subsequently  numerous  investigators  have  written  upon  the 
subject  of  congenital  syphilis  and  with  it  no  other  name  is  more 
prominently  linked  than  that  of  Sir  John  Hutchinson  (1828-1913), 
who  probably  is  best  known  on  account  of  his  description  of  the 
notched,  peg-shaped  incisor  teeth  in  congenital  syphilis  ("Hutchin- 
son teeth*"). 

ETIOLOGY. 

In  discussing  the  etiology  of  congenital  syphilis  the  question 
naturally  arises  as  to  whether  the  infection  is  due  to  a  syphilitic 
father,  a  syphilitic  mother  or  to  both.  Until  comparatively  recently 
most  authorities  were  agreed  that  if  either  parent  were  infected  a 
syphilitic  child  could  result,  that  paternal  infection  was  the  most 
frequent  and  that  if  both  parents  were  luetic  the  chances  of  syphi- 
litic offspring  were  increased.  It  was  thought  that  the  syphilitic 
virus  could  be  carried  in  the  spermatozoa  and  thus  infect  the  ovum 
or  that  the  fetus  could  be  infected  in  utero  from  the  semen. 

These,  however,  certainly  are  false  premises,  for  although  as 
pointed  out  in  the  chapter  on  Etiology  of  Acquired  Syphilis,  the  semen 
in  some  cases  of  syphilis  has  been  found  to  be  infective  for  animals, 
this  does  not  necessarily  mean  that  the  treponema  is  present  in 
the  spermatozoon.  In  fact  from  the  relative  sizes  of  the  syphilitic 
organism  and  the  spermatozoon,  as  well  as  the  active  motility  of 
the  former,  it  would  seem  to  preclude  such  a  possibility.  Further, 
while  it  is  admitted  that  the  semen  might  in  some  cases  carry  the 
syphilitic  organism  to  the  ovum,  although  it  is  doubtful  if  this 

1  Cited  by  Marshall:  Syphilology  and  Venereal  Disease,  New  York,  1906,  p.  317. 
^  Cited  by  Sturgis  in  Morrow's  System  of  Genito-urinary  Diseases,  Syphilology, 
and  Dermatology,  New  York,  1898,  p.  604. 

3  Cited  by  Still  in  Power  and  Murphy's  System  of  Syphilis,  London,  1908,  i,  p.  283. 
^  Hutchinson:  Brit.  Med.  Jour.,  1861,  p.  515. 


ETIOLOGY  369 

could  occur  when  the  ovum  is  in  the  Fallopian  tube,  its  usual  loca- 
tion upon  fecundation,  it  seems  extremely  improbable  that  the 
ovum  could  develop  with  even  a  single  Treponema  pallidum 
within  it. 

In  regard  to  the  subsequent  infection  of  the  embryo  or  fetus 
in  utero  direct  from  the  father,  it  need  only  be  mentioned  that  the 
membranes  at  a  very  early  date  effectually  close  the  uterine  canal. 

From  the  above  evidence  it  would  seem  that  direct  paternal 
infection  is  impossible. 

Congenital  syphilis  can  therefore  occur  only  through  an  infected 
mother,  and  this  only  after  conception  either  by  the  carrying  of 
the  organisms  by  the  blood  through  the  placenta  or  by  infection 
from  a  diseased  placenta,  or  finally,  by  direct  contact  with  syphilitic 
lesions  of  the  genitals  at  the  time  of  birth. 

The  outcome  of  the  conception  of  a  syphilitic  woman  presents 
several  possibilities,  namely: 

1.  Infection  of  the  embryo  or  fetus  in  utero  or  of  the  child  at 
the  time  of  birth;  2,  the  death  of  the  embryo  or  fetus  due  to  a 
markedly  syphilitic  placenta;  3,  the  transmission  of  certain  unknown 
traits  to  the  embryo  which  cause  abnormal  development,  without 
actual  infection  by  the  Treponema  pallidum  occurring;  and  4,  the 
birth  of  a  perfectly  healthy  child.  What  factor  or  factors  serve 
as  determining  causes  it  is  impossible  to  say. 

Of  the  first  possibility  several  results  may  be  seen,  depending 
to  a  large  extent  upon  the  age  of  the  embryo  or  fetus  when  infection 
takes  place. 

If  infection  occurs  very  early,  the  development  of  the  embryo 
usually  will  cease  and  abortion  follow.  Later  infection  may  permit 
development  to  continue  and  a  living  but  syphilitic,  weak  and  puny 
child  be  born  prematurely.  This  child  may  die  directly  following 
birth  or  soon  after.  The  child  may  develop  for  some  time,  even  to 
term,  and  stillbirth  occur.  A  further  possibility  is  the  birth  of 
a  full-term  child  showing  either  marked  or  very  slight  manifesta- 
tions of  syphilis  or  none  at  all  but  developing  symptoms  a  few  weeks 
later,  or  finally  the  so-called  "syphilis  hereditaria  tarde"  may 
occur,  the  syphilitic  manifestations  apparently  not  showing  for 
months  or  even  years  after  birth. 

These  latter  cases,  however,  must  be  looked  upon  with  consider- 
able doubt,  as  in  all  probability  earlier  manifestations  of  the  con- 
genital disease  occurred  and  were  unnoticed  or  they  may  have  been 
cases  of  acquired  syphilis  with  slight  and  unnoticed  early  mani- 
festations. 

The  time  at  which  the  embryo  or  fetus  may  become  infected 
will  depend  upon  whether  the  mother  is  suffering  with  syphilis  at 
the  time  of  conception  or  is  infected  subsequently,  and  also  upon 
24 


370  CONGENITAL  SYPHILIS 

the  severity  of  the  disease  in  the  mother.  It  is  almost  self-evident 
that  if  the  mother  is  suffering  with  a  marked  treponemia  at  the 
time  of  conception  the  embryo  soon  will  become  infected.  If,  on 
the  other  hand,  the  syphilis  of  the  mother  is  in  a  comparatively 
quiescent  state  with  treponemata  in  the  blood  only  in  small  number, 
if  at  all,  the  chances  of  infection  are  lessened.  Formerly  the  dictum 
of  Ricord,  that  only  until  the  sixth  month  can  the  mother  trans- 
mit syphilis  acquired  during  pregnancy  to  the  offspring,  after  which 
time  they  are  safe,  was  religiously  followed,  but  in  recent  years  well- 
authenticated  cases  of  the  mother  being  infected  in  the  eighth 
or  even  the  ninth  month  of  pregnancy  and  bearing  syphilitic  children 
have  been  reported. 

The  second  possibility  of  the  conception  of  a  syphilitic  woman, 
the  death  of  the  fetus  in  utero,  due  to  a  diseased  placenta  is  brought 
about,  not  by  infection,  but  by  lack  of  nutrition,  and  is  followed 
by  abortion. 

The  third  possibility,  the  transmission  of  certain  traits  to  the 
child  without  causing  infection  with  the  organism  of  syphilis,  may 
be  as  serious  as  the  actual  transmission  of  the  disease.  In  such  cases 
again  the  development  of  the  embryo  may  be  retarded,  abortion 
or  stillbirth  may  occur^  or  the  child  may  be  premature  or  born  at 
full  term  but  with  certain  abnormalities  of  mind  and  body.  Such 
a  condition  may  also  be  brought  about  by  a  syphilitic  father  without 
the  necessity  of  the  mother  having  the  disease,  although  in  all 
probability  it  is  more  frequent  when  both  parents  are  syphilitic. 
The  pathogenesis  of  such  a  condition  is  not  known.  It  may  be  that 
it  is  due  to  the  toxins  of  the  treponemata  acting  upon  the  spermato- 
zoon or  ovum  or  both  and  so  changing  them  chemically  or  physi- 
cally, or  by  lowering  their  vitality,  that  they  fail  to  develop  in  a 
normal  manner.  It  is,  of  course,  possible  that  there  may  be  a  com- 
bination of  the  first  and  third  possibilities,  that  is,  a  true  syphilitic 
infection  from  the  mother  may  be  superimposed  in  utero  upon  the 
child  which  is  already  developing  abnormally  from  the  traits  trans- 
mitted through  the  ovum  'or  spermatozoon. 

The  possibility  of  the  conception  of  a  syphilitic  woman  that  she 
may  bear  a  normal  child  needs  no  further  comment  but  that  such 
a  child  may  follow  or  precede  a  syphilitic  one. 

Secondary  Etiological  Factors. — ^That  there  are  any  secondary 
factors  such  as  race,  age,  climate,  etc.,  which  have  any  bearing 
upon  the  etiology  of  congenital  syphilis  has  not  been  shown. 

Moore^  found  of  582  hospital  admissions  of  negro  infants  and  chil- 
dren, 52  or  8.9  per  cent,  were  clinically  suffering  from  hereditary 
syphilis,  and  of  225  white  infants  and  children  only  7  or  3.1  per 

1  Southern  Med.  Jour.,  1915,  viii,  p.  946. 


ETIOLOGY  371 

cent,  were  syphilitic.  This,  however,  does  not  prove  that  syphiHtic 
negroes  are  more  prone  to  produce  syphiHtic  children  than  whites, 
but  merely  shows  that  syphilis  is  more  prevalent  in  the  negro  race. 

Syphilis  in  the  Third  Generation. — ^That  hereditary  syphilitics 
may  in  turn  produce  syphilitic  children  is  undoubted. 

Hutchinson^  expressed  his  disbelief  in  such  an  occurrence,  although 
he  cited  a  case  of  his  own  which  was  probably  one  of  syphilis  in 
the  third  generation.  Numerous  other  syphilographers  have  written 
pro  and  con  upon  this  subject  but  until  the  advent  of  the  Wasser- 
mann  reaction  the  evidence  for  neither  side  of  the  question  was 
absolutely  convincing. 

Glomset^  recently  has  reported  two  cases,  one  of  which  undoubt- 
edly was  an  instance  of  syphilis  in  the  third  generation,  while  the 
evidence  in  the  other  case  is  at  least  very  suggestive. 

In  the  first  case  reported,  Glomset  states  that  the  first  born  of 
a  young  couple  was  diagnosed  syphilitic,  clinically,  by  two  physicians 
and  by  a  positive  Wassermann,  and  later  died  in  spite  of  treatment. 
Both  of  the  parents  denied  the  possibility  of  infection  but  sub- 
mitted to  Wassermann  tests,  the  father's  blood  upon  repeated 
examinations  giving  negative  results  and  the  mother's  positive. 
Following  this  the  mother  in  order  to  clear  herself,  brought  an 
older  sister  and  a  younger  brother  for  tests,  both  of  which  proved 
to  be  positive.  Then  the  children  brought  their  father  for  a  Wasser- 
mann which  was  negative,  but  soon  after,  the  man's  wife,  the  grand- 
mother of  the  child  originally  seen,  died  from  what  was  diagnosed 
gumma  of  the  brain,  and  blood  collected  less  than  twenty  minutes 
after  death  gave  a  positive  reaction. 

1  Steadman:  Twentieth  Century  Practice  of  Medicine,  New  York,  1899,  xviii, 
p.  395. 

2  Jour.  Am.  Med.  Assn.,  1915,  Ixv,  p.  682. 


CHAPTER  XXI. 
GENERAL  PATHOLOGY  AND  CLINICAL  HISTORY. 

In  general  it  may  be  said  that  the  pathological  picture  in  con- 
genital syphilis  is  the  same  as  in  the  acquired  form,  however,  there 
are  certain  differences  which  must  be  described.  The  chancre,  of 
course,  is  not  present  in  congenital  syphilis  except  where  the  child 
is  infected  in  passing  through  the  birth  canal,  and  even  if  present 
may  pass  unnoticed.  While  all  the  other  lesions  of  acquired  syphilis 
may  be  duplicated  in  the  congenital  form,  as  a  rule  they  are  milder 
in  type,  though  of  more  extensive  distribution.  Gummata  in  con- 
genital syphilis  are  comparatively  rarely  seen  but  connective-tissue 
production  is  marked  in  the  various  organs,  especially  in  the  liver, 
and  is  the  result  of  a  regenerative  proliferation  of  the  fibroblasts. 

Placenta. — While  the  placenta  is  composed  partly  of  maternal 
and  partly  of  fetal  tissue,  it  is  nevertheless  a  product  of  conception 
and  therefore  its  affection  with  syphilis  is  discussed  at  this  place. 
The  syphilitic  placenta  is  larger  and  heavier  than  normal,  its  weight 
sometimes  being  one-fourth  to  one-third  that  of  the  fetus,  while 
the  normal  proportion  is  one-sixth.  This  increase  in  weight  is 
caused  by  a  hyperplasia  of  the  chorionic  villi,  chiefly  due  to  an 
increase  in  the  connective  tissue  surrounding  the  bloodvessels  which 
show  endarteritis.  Treponemata  have  been  found  by  numerous 
investigators.  The  syphilitic  placenta  is  more  friable  than  the 
normal  organ  and  is  of  a  light  red  color,  showing  pale  yellowish 
patches.  It  may  be  the  seat  of  hemorrhages  which  cause  a  partial 
separation. 

The  umbilical  cord  also  may  be  the  seat  of  the  syphilitic  process, 
the  Treponema  pallidum  having  been  demonstrated  numerous 
times.    An  endarteritis  and  even  thrombosis  may  occur. 

Course  of  Congenital  Syphilis. — As  pointed  out  above,  infants 
may  be  born  with  active  manifestations  of  syphilis,  or  without  such 
manifestations  which  develop  within  a  few  weeks,  or  finally  the 
so-called  syphilis  hereditaria  tarde  may  occur. 

The  typical  picture  of  an  infant  born  with  active  syphilitic 
manifestations  is  a  pitiable  sight.  It  is  small,  weasened,  thin  and 
weak.  The  skin  is  wrinkled  and  flabby,  has  been  described  as  of 
a  cafe  au  lait  color,  and  may  be  the  seat  of  syphilodermata.  The 
eyes  are  more  or  less  sunken  and  inflamed  and  the  general  appear- 
ance has  been  likened  to  a  "little  old  man."    There  is  more  or  less 


PLACENTA  373 

involvement  of  the  mucous  membrane  of  the  nose,  causing  the  so- 
called  "  snuffles,"  and  the  cry  is  hoarse,  due  to  laryngeal  involvement. 
There  may  also  be  pseudoparalysis,  due  to  inflammation  of  one 
of  the  bones  near  the  epiphysis  or  there  may  be  various  symptoms, 
due  to  involvement  of  the  central  nervous  system.  It  is  rare  for 
such  a  marked  picture  to  be  observed  in  living  infants  but  some  of 
the  symptoms  may  be  present. 

On  the  other  hand,  it  is  more  frequent  for  a  syphilitic  child  to  be 
born  apparently  normal.  In  a  variable  time,  from  a  few  days  to 
several  months,  it  begins  to  fall  away  and  the  various  symptoms 
outlined  above,  snufHes,  hoarse  cry,  syphilodermata,  pseudo- 
paralysis, etc.,  may  make  their  appearance.  Miller,^  in  an  analysis 
of  1000  cases,  states  that  the  first  symptoms  developed  during  the 
first  month  in  64  per  cent,  (by  weeks;  first,  8.5  per  cent.,  second, 
13.8  per  cent.,  third,  24  per  cent.,  fourth  17.7  per  cent.)  and  during 
the  second  month  in  22  per  cent.  For  a  longer  period  than  two 
months  accurate  observations  were  not  made.  In  addition  to  these 
such  symptoms  as  stomatitis,  nephritis,  enlarged  spleen  and  liver, 
retinitis,  iritis,  various  bone  lesions,  alopecia,  etc.,  may  make  their 
appearance.  If  the  patient  recovers  from  these  symptoms  he  may 
remain  in  apparent  health  for  several  years  only  to  develop  lesions 
which  resemble  the  later  manifestations  of  acquired  syphilis,  such 
as  gummata  of  the  skin  or  viscera,  as  well  as  certain  lesions  rarely 
seen  in  the  acquired  form  of  the  disease.  The  most  typical  of  these 
are  interstitial  keratitis  and  Hutchinson's  teeth. 

In  the  so-called  syphilis  hereditaria  tarde,  symptoms  apparently 
do  not  develop  for  years  after  birth,  but  in  all  probability  they  are 
present  either  at  or  soon  after  birth  and  are  so  slight  as  to  pass 
unnoticed.  Such  symptoms  as  rhinitis  or  a  rash  may  have  existed 
and  little  or  no  attention  given  it,  but  it  is  entirely  within  the  range 
of  possibility  that  no  outward  manifestations  are  present  and  the 
viscera  alone  are  affected.  Finally,  as  pointed  out  above,  the  pos- 
sibility of  acquired  syphilis  with  slight  early  symptoms  must  be 
kept  in  mind. 

The  year  at  which  syphilis  tarde  is  said  to  make  its  appearance 
most  frequently  is  the  twelfth,  although  it  may  appear  earlier  or 
in  rare  instances  much  later.  Bellizzi^  reports  a  case  in  which  appar- 
ently perfect  health  was  enjoyed  until  the  age  of  thirty-eight  was 
reached,  at  which  time  cardiovascular  disease  with  positive  Was- 
sermann  both  on  the  blood  and  pleural  effusion  developed. 

Other  cases  of  extremely  late  development  of  symptoms  of  con- 
genital syphilis  have  been  reported,  but  only  those  which  have 
carefully  been  followed  from  birth  should  be  considered  as  authentic. 

1  Jahrb.  f.  Kinderh.,  1888,  xxvii,  p.  359. 

2  Reforma  med.,  1915,  xxxi,  p.  174. 


374        GENERAL  PATHOLOGY  AND  CLINICAL  HISTORY 

Lymphatic  Glands. — That  the  lymphatic  glands  are  affected 
by  the  Treponema  pallidum  in  congenital  syphilis  as  well  as  in  the 
acquired  type  is  well  known,  although  most  writers  have  little  or 
nothing  to  say  on  the  subject.  The  epitrochlear,  inguinal  and 
cervical  are  the  glands  most  frequently  involved,  although  any  of 
the  lymphatic  glands  of  the  body  may  be  affected.  The  epitroch- 
lears  are  enlarged  on  one  or  both  sides  in  from  80  to  90  per  cent, 
of  cases,  while  the  inguinal  and  cervicals  are  less  frequently  involved. 
Enlargement  of  the  various  glands  due  to  their  proximity  to  ulcera- 
tive skin  lesions  is  not  rare.  As  a  rule  the  glands  are  only  moder- 
ately enlarged,  rarely  becoming  larger  than  a  bean,  although  the 
size  of  an  ordinary  marble  may  be  attained.  The  pathological 
picture  differs  in  no  respect  from  that  observed  in  acquired  syphilis. 

Cutaneous  Lesions. — Nearly  all  of  the  syphilodermata  of  the 
acquired  disease  may  be  duplicated  in  congenital  syphilis,  although 
they  are  usually  somewhat  modified  and  some  types  are  less  often 
observed,  while  the  bullous  syphiloderm  is  much  more  frequent  than 
in  acquired  syphilis. 

Macular  Syphiloderm. — An  erythematous  macular  eruption  is  one 
of  the  most  frequently  observed  of  the  syphilodermata  of  the  con- 
genital type  of  the  disease.  The  macules  rarely  are  circumscribed, 
but  more  often  are  diffuse  and  usually  are  of  a  dull  ham  color, 
although  a  yellowish  brown  sometimes  is  observed.  The  true 
macular  eruption  is  not  elevated  above  the  surrounding  skin.  The 
circumscribed  macules  are  irregularly  round  in  shape  while  the 
diffuse  eruption  occurs  in  large  irregular  blotches.  The  most  fre- 
quent location  is  the  genitocrural  region,  usually  also  involving  the 
buttocks  and  sometimes  passing  down  the  thighs.  The  eruption  not 
infrequently  is  seen  on  the  face;  the  chin,  upper  lip  and  the  area 
between  the  eyes  and  above  the  nose  being  the  most  frequent 
locations. 

The  macular  eruption  occasionally  is  the  first  evidence  of  the 
disease,  although,  as  a  rule,  it  is  accompanied  by  other  symptoms 
such  as  snuffles.  It  is  rarely  or  never  seen  at  birth  and  usually 
makes  its  appearance  during  the  first  few  weeks  of  life,  but  may  be 
delayed  two,  three,  or  more  months. 

When  the  borders  of  the  lips  and  the  cutaneous  surface  around 
the  nostrils  and  around  the  eyes,  where  the  action  of  the  muscles 
keep  the  skin  in  motion,  are  attacked  by  the  diffuse  macular  syphilo- 
derm fissures,  rhagades  are  formed  which  may  leave  permanent 
scars  and  are  very  suggestive  of  congenital  syphilis.  This  type 
of  eruption  is  somewhat  persistent,  and  even  in  spite  of  treatment 
new  lesions  may  develop.  In  milder  cases  the  eruption  in  a  short 
time  begins  to  fade  and  gradually  disappears. 

The  macular  syphilodermata  in  congenital  syphilis  sometimes 


VESICULAR  SYPHILODERM  375 

must  be  differentiated  from  erythema  intertrigo.  The  skin  in  the 
latter  condition  is  of  a  lighter  red  color  than  the  syphilitic  eruption, 
and  the  color  disappears  on  pressure,  which  it  does  not  altogether 
do  in  syphilis,  in  which  condition  a  yellowish  tint  to  the  skin  is  left. 
However,  other  evidences  of  congenital  syphilis  usually  are  present 
as  well  as  positive  laboratory  jfindings. 

Papular  Syphiloderm. — A  true  papular  eruption  without  macules 
is  exceedingly  rare  in  congenital  syphilis. 

When  this  type  of  lesion  does  occur  it  is  nearly  always  as  a 
recurrence,  being  observed,  as  a  rule,  between  the  sixth  and  twelfth 
months,  although  it  may  be^een  as  late  as  the  third  or  fourth  year. 

This  type  of  eruption  is  of  a  brownish  color  and  of  a  peculiar 
glossy  appearance.  The  papules,  which  are  always  few  in  number, 
are  sometimes  scattered  and  sometimes  occur  in  groups.  The  most 
frequent  locations  are  the  back  of  the  neck,  the  back,  the  forehead 
and  rarely  on  the  arms  and  legs.  They  are  usually  most  refractory 
to  treatment.  Moist  papules  around  the  anus,  genitalia  and  in  the 
the  folds  of  the  skin  comparable  to  these  lesions  in  acquired  syphilis 
are  not  infrequent. 

Maculopapular  Syphiloderm. — The  so-called  maculopapular  erup- 
tion certainly  is  the  most  frequently  observed  of  all  the  syphilo- 
dermata  of  the  congenital  form  of  the  disease,  and  in  quite  a 
large  percentage  of  cases  is  the  first  symptom  of  the  disease  to 
appear.  Some  of  the  eruptions  are  macular,  some  papular  and  some 
truly  maculopapular. 

As  with  the  macular  eruptions,  they  may  be  circumscribed  or 
diffuse,  the  latter  being  due  to  a  confluence  of  several  discrete  lesions. 
The  color,  as  a  rule,  is  the  typical  dark  red  ham  hue,  although  a  lighter 
shade  may  be  observed  when  the  eruption  is  seen  early.  They  are 
slightly  elevated  above  the  surrounding  skin,  and  in  size  and  shape 
resemble  the  macular  eruptions.  The  lesions  are  distributed  mainly 
on  the  lower  limbs,  the  flexor  surfaces  of  the  arms,  the  neck,  the 
chin  and  the  face,  although  scarcely  any  portion  of  the  body  is 
exempt.  The  palms  of  the  hands  and  the  soles  of  the  feet  quite 
frequently  are  involved  where  the  eruption  appears  thicker,  tenser 
and  of  a  lighter  color. 

The  date  of  the  appearance  of  the  eruption  corresponds  to  that 
of  the  true  macular  type.  As  a  rule  the  eruption  disappears  by 
absorption,  although  desquamation  of  these  lesions  is  not  uncommon, 
the  skin  sometimes  peeling  in  large  flakes. 

Vesicular  Syphiloderm, — ^This  type  of  eruption  in  congenital 
syphilis,  as  in  the  acquired  form  of  the  disease,  is  exceedingly  rare 
and  when  it  does  occur  usually  is  in  association  with  a  pustular  or 
bullous  eruption.     Two   cases  have  been  reported  by  Grindon,^ 

1  Jour.  Cut.  Dis.,  1910,  xxxviii,  p.  284. 


376        GENERAL  PATHOLOGY  AND  CLINICAL  HISTORY 

who  briefly  reviews  the  subject.  One  case  sliowed  many  mihary 
and  the  other  many  pin-head-sized  vesicles. 

Bullous  Syphiloderm. — This  lesion,  often  eroneously  called  syphi- 
litic pemphigus,  which  is  the  rarest  of  all  skin  lesions  of  acquired 
syphilis,  is  of  comparatively  frequent  occurrence  in  the  congen- 
ital type,  being  found  by  Miller^  in  25  per  cent,  of  cases.  The 
lesions  usually  are  of  large  size,  from  1  to  3  cm.  in  diameter. 
They  are  of  a  copper  color,  are  seated  either  upon  an  ulcerated  or 
eroded  base  and  may  be  surrounded  by  an  infiltrated  copper-colored 
rim.  As  a  rule  they  are  flacid  but  they  may  be  tense  and  contain 
a  yellowish,  cloudy  fluid,  often  becoming  purulent  or  bloody. 

The  most  frequent  location  of  the  bullous  syphiloderm  is  upon 
the  palms  of  the  hands  and  the  soles  of  the  feet,  to  which  locations 
it  may  be  limited,  or  it  may  be  found  on  nearly  any  portion  of  the 
body  surface. 

This  lesion  is  seen  earlier  than  any  of  the  other  syphilodermata 
of  congenital  syphilis  not  infrequently  developing  in  intra-uterine 
life  and  being  present  at  birth.  It  may,  however,  not  make  its 
appearance  for  two  or  three  to  five  or  six  weeks. 

The  bullae,  as  a  rule,  soon  burst,  leaving  an  eroded  or  ulcerating 
surface  which  later  may  be  covered  by  a  greenish  scab.  On  section 
the  bullous  syphiloderm  is  seen  to  be  made  up  of  two  chambers 
containing  fluid.  First,  the  superficial  layers  of  the  epidermis  are 
distended  with  a  large  amount  of  fluid  between  them  and  the  rete 
Malpighii,  and  second  the  rete  is  detached  in  places  by  an  accumu- 
lation of  fluid  between  it  and  the  papillary  layer.  Microscopically, 
a  uniform  inflammatory  proliferation  of  the  cells  of  the  papillary 
layer  is  observed.  This  is  seen  to  follow  the  bloodvessels.  Num- 
erous investigators  have  reported  the  finding  of  treponemata 
both  in  the  fluid  of  the  blebs  and  in  the  papillary  layer. 

The  bullous  syphiloderm  must  be  distinguished  from  pemphigus. 
The  latter  condition  rarely  appears  before  the  end  of  the  second 
week  of  life,  while  the  syphilitic  lesion  is  common  at  birth  or  soon 
after.  The  syphilitic  eruption,  also,  has  a  predilection  for  the  palms 
of  the  hands,  or  the  soles  of  the  feet,  which  regions  pemphigus 
rarely  attacks.  The  contents  of  the  syphilitic  bullae  soon  become 
purulent,  which  does  not  occur  with  the  blebs  of  pemphigus.  With 
the  syphilitic  eruption  other  manifestations  of  syphilis  also,  as  a 
rule,  are  present,  although  the  final  diagnosis  may  have  to  rest  upon 
the  finding  of  the  treponemata  in  the  lesions  or  other  positive 
laboratory  evidence. 

The  pustular  syphiloderm  is  a  rare  type  in  congenital  syphilis 
and  when  pustules  do  occur  they  usually  are  the  result  of  purulent 
change  taking  place  in  the  vesicular  or  bullous  lesions.     Never- 

1  Jahrb.  f.  Kinderh.,  1888,  xxvii,  p.  359. 


BULLOUS  SYPHILODERM 


377 


theless   occasionally  true  pustules  may  be  seen,  especially  around 
the  mouth  or  anus,  usually  in  association  with  the  maculopapular 


Fig.  73. — Congenital  syphilis  showing  papulopustular  syphiloderm.     (Holt.) 


eruption.    Sometimes  the  contents  of  the  pustule  upon  drying  forms 
crusts  very  much  resembling  the  rupia  of  acquired  syphilis. 


378 


GENERAL  PATHOLOGY  AND  CLINICAL  HISTORY 


Nodular  Syphiloderm. — This  type  of  syphilitic  eruption  also  is 
rare  in  the  congenital  form  of  the  disease.  When  it  does  occur  it 
is,  as  a  rule,  of  late  appearance,  usually  being  seen  as  a  recurrence 
several  years  after  birth.  It  may,  however,  develop  as  early  as 
the  sixth  month.  This  lesion  differs  in  no  respect  from  the  same 
type  of  lesion  in  acquired  syphilis. 


Fig.  74. — Chancre  of  lip  with  pustular  syphiloderm  in  child. 


Gummatous  Syphiloderm. — Gummata  of  the  skin  in  congenital 
syphilis  differ  in  no  respect  from  these  lesions  in  the  acquired  form 
of  the  disease.  They  are  seen  most  frequently  upon  the  front  of 
the  leg  or  on  the  face.  In  the  latter  location  they  may  produce 
considerable  destruction  of  tissue  by  ulcerating.  The  gummatous 
syphiloderm  is  rare  in  early  congenital  syphilis  but  is  not  infrequent 
later  as  a  recurrence  or  as  one  of  the  symptoms  of  syphilis  hereditaria 
tarde. 


GENERAL  SYMPTOMS  379 

Aside  from  the  syphilodermata  the  skin  in  early  congenital 
syphilis  may  present  a  wrinkled,  paper-like  appearance. 

Syphilis  of  the  Appendages  of  the  Skin. — ^Alopecia. — Alopecia 
may  occm*  in  congenital  syphilis  as  in  acquired  syphilis,  although 
complete  baldness  is  rare.  The  eyebrows  may  be  attacked  as  well 
as  the  hair  of  the  head.  Alopecia  may  occur  as  an  early  symptom 
in  association  with  the  skin  lesions  or  it  may  appear  later  and  in 
syijhilis  tarde  it  may  be  a  prominent  symptom.  It  must  be  borne 
in  mind  that  not  infrequently  the  first  hair  of  the  newborn  falls 
out  when  no  syphilis  is  present.  StilP  states  that  an  unusually 
abundant  crop  of  dark  hair  at  birth  or  appearing  soon  after  has 
been  described  as  a  symptom  of  congenital  syphilis,  and  that  this 
"  syphilitic  mop"  or  "wig"  has  been  observed  by  him  in  4  per  cent, 
of  his  cases. 

Onychia.^ — Onychia  occurs  in  congenital  syphilis  as  a  drying  and 
shrivelling  process.  It  has  been  suggested  that  the  nail  appears  as 
if  it  had  been  pinched  together  laterally,  with  a  high  ridge  in  the 
centre  resembling  a  claw.  The  nails  of  either  the  fingers  or  the 
toes  may  be  involved  and  sometimes  all  the  nails  are  affected. 

Paronychia. — Paronychia  also  may  occur,  the  nail  becoming 
loosened  and  detached. 

These  conditions,  as  a  rule,  are  manifestations  of  the  first  few 
months  of  the  disease,  but  may  be  observed  later  in  its  course. 

Mucous  Membranes. — Not  all  of  the  syphilomycodermata  seen 
in  acquired  syphilis  are  found  in  the  hereditary  form  but  the  erosive 
yapular  lesions  or  mucous  yatch  not  infrequently  is  observed  in  the 
mouth.  Condylomata  and  ulcerative  gummatous  lesions  also  are 
not  rare.  The  mucous  patch  and  condylomata  are  types  of  early 
hereditary  lesions,  while  gummata  are  of  late  appearance.  The 
lesions  differ  in  no  respect  from  the  similar  lesions  in  acquired 
syphilis.  Syphilitic  involvement  of  the  mucous  membranes  of  the 
nose  will  be  discussed  under  Syphilis  of  the  Respiratory  Tract. 

General  Symptoms.^ — Temperature. — The  more  marked  of  the 
syphilodermata  of  congenital  syphilis  usually  are  accompanied  by 
more  or  less  fever.  The  temperature  rarely  rising  above  39°  C. 
(102°  F.)  and  when  the  eruption  is  not  severe  may  be  subnormal. 
The  jiulse  rate  may  or  may  not  be  in  proportion  to  the  temperature, 
although  it  rarely  reaches  more  than  110  to  120  beats  per  minute. 

Blood. — There  is  more  or  less  anemia  in  practically  all  cases  of 
congenital  syphilis,  especially  is  this  true  in  early  cases  with  active 
manifestations.  Chiaravalloti^  examined  the  blood  of  150  cases 
of  varying  ages  and  found  that  the  hemoglobin  varied  from  12  to 
75  per  cent.,  with  an  average  of  56.8  per  cent.,  while  the  number 

1  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  i,  p.  303. 

2  Pediatria,  1914,  xxii,  p.  881. 


380        GENERAL  PATHOLOGY  AND  CLINICAL  HISTORY 

of  erythrocytes  was  lower  than  normal.  Marked  variations  in  the 
differential  leukocyte  count  were  observed,  though  nothing  char- 
acteristic was  found. 

Hazen^  in  an  examination  of  but  5  cases  of  congenital  syphilis 
states  that  such  cases  do  not  necessarily  show  a  high  lymphocyte 
count. 

Hochsinger^  states  that  aside  from  the  diminution  in  the  per- 
centage of  hemoglobin  and  the  number  of  erythrocytes  observed 
in  early  congenital  syphilis  many  normoblasts  are  observed  as 
well  as  a  leukocytocia  which  especially  affects  the  myelocytes 
and  eosinophiles. 

1  Jour.  Cut.  Dis.,  1913,  xxxi,  p.  618. 

2  Pfaundler  and  Schlosemann :  Diseases  of  Children,  Philadelphia  and  London, 
1912,  ii,  p.  534. 


CHAPTER  XXII. 
REGIONAL  SYPHILIS. 

SYPHILIS    OF    THE    CIRCULATORY    SYSTEM. 

Heart. — ^Warthin^  in  an  excellent  study  of  12  cases  of  congenital 
syphilis  states  that  in  the  majority  of  early  cases  the  heart  was 
found  large  and  dilated,  in  the  others  normal  in  size  or  smaller  than 
normal.  The  heart  muscle  was  usually  pale  or  contained  lighter 
areas,  while  the  walls  were  generally  thicker  than  normal.  The 
muscle  seemed  moister,  softer  and  more  translucent  than  normal. 
In  some  hearts  nothing  pathological  could  be  detected  by  the  gross 
appearance.  The  older  cases  showed  grossly,  mitral  endocarditis, 
with  insufficiency,  compensatory  hypertrophy  and  dilatation,  with 
no  evidence  of  myocarditis  until  microscopic  examinations  were 
made. 

Microscopically,  all  the  cases  showed  throughout  the  myocardium 
numerous  or  few  light  staining  patches  separating  or  replacing  the 
muscle  fibers  and  made  up  of  a  fibroblastic  or  myxomatous  tissue. 
These  contained  a  delicate  granular  or  fibrillar  reticulum  in  which 
were  found  numerous  cells  of  lymphocyte  or  plasma-cell  type,  as  well 
as  numerous  large  epithelioid  cells  with  abundant  pink-staining 
granular  protoplasm  and  pale  nuclei.  These  latter  cells  presented 
various  sizes  and  shapes  as  well  as  vacuolization,  fragmentation  and 
loss  of  nucleus.  The  heart-muscle  fibers  showed  a  peculiar  pale 
coagulation  degeneration  or  necrosis  in  the  neighborhood  of  the 
fibroblastic  proliferation.  The  protoplasm  was  seen  to  have  lost  its 
striations  and  its  ability  to  take  the  eosin  stain,  while  the  nuclei  were 
large  and  swollen  and  took  the  hematoxylin  poorly.  The  smaller 
bloodvessels  showed  an  epithelioid  proliferation  of  their  walls  and 
often  the  lumina  were  filled  with  cells  similar  to  those  of  the  stroma. 
The  larger  vessels,  both  arteries  and  veins,  showed  varying  degrees 
of  thickening,  especially  in  the  intima  and  adventitia.  Obliterating 
endarteritis  was  not  common,  in  fact  the  interstitial  changes  were 
in  all  cases  much  more  marked  than  the  arterial  changes.  Stained 
by  Levaditi's  method  the  fibroblastic  epithelioid  areas  of  the  heart 
wall  were  found  crowded  with  treponemata. 

From  the  above  evidence  Warthin  concludes  that  there  exists 
not  infrequently  in  congenital  syphilis  a  characteristic  form  of 

1  Am.  Jour.  Med.  Sc,  1911,  cxlii,  p.  398. 


382  REGIONAL  SYPHILIS 

interstitial  myocarditis  due  to  the  localization  of  colonies  of  Trepon- 
ema pallidum,  which  in  some  instances  is  the  only  evidence  of  the 
disease  and  sometimes  cannot  be  recognized  except  by  miicroscopic 
examination.  Only  in  the  older  cases  of  Warthin's  series  were  symp- 
toms of  heart  disease  present  and  in  them  syphilis  was  not  suspected. 

Arteries. — xiortitis  with  or  without  aneurysm  has  been  noted  in 
congenital  syphilis  and  differs  little,  if  at  all,  from  that  observed 
in  the  acquired  type.  Endarteritis  and  periarteritis  of  the  smaller 
arteries  also  are  observed. 

Veins. — The  veins  in  congenital  syphilitics  seem  to  be  peculiarly 
weak  and  dilatation  of  the  superficial  veins  of  the  scalp  often  are 
noticed  in  young  infants.  Later  in  the  course  of .  congenital  syphilis 
varicose  veins,  especially  of  the  legs,  are  common.  These  frequently 
lead  to  ulceration  and  the  combination  of  syphilitic  characteristics 
and  those  of  varicose  ulcers  often  is  most  refractory  to  treatment. 

SYPHILIS    OF    THE   RESPIRATORY    TRACT. 

Rhinitis  is  one  of  the  most  frequent  affections  in  early  congenital 
sj'philis.  It  is  seen,  as  a  rule,  during  the  first  three  months  of  life 
and  not  infrequently  has  been  observed  on  the  first  day  of  life. 
The  most  typical  symptom  of  this  condition  is  the  so-called 
"snuffles"  or  snuffling  respiration  which  describes  the  condition 
quite  accurately.  At  first  there  is  little  or  no  discharge,  there 
being  merely  an  obstruction  to  the  nasal  passages  due  to  swelling 
of  the  mucosa,  especially  of  the  inferior  turbinate  bone.  Soon, 
however,  a  mucotis  discharge  makes  its  appearance  which  may 
become  purulent,  or  even  stained  with  blood,  depending  upon  the 
severity  of  the  process.  This  obstruction  of  the  nasal  passages 
makes  nursing  difficult  and  often  the  head  is  retracted  in  a  position 
of  opisthotonos  to  aid  respiration.  If  the  condition  is  left  untreated 
and  the  process  extends  to  the  cartilage,  bone  ulceration  and 
even  necrosis  may  occur  and  marked  deformities  result.  These 
deformities,  however,  are  noted  more  frequently  later  in  the  course 
of  the  disease  as  a  result  of  gummata.  Such  deformities  as  saddle- 
nose,  perforated  palate,  etc.,  are  seen  and  are  comparable  to  similar 
deformities  in  acquired  syphilis. 

Larynx. — Syphilitic  laryngitis  usually  occurs  in  the  congenital 
type  of  the  disease  as  an  accompaniment  of  rhinitis.  It  is  not,  how- 
ever, as  frequent  as  the  latter  condition.  The  principle  symptom 
is  a  hoarse,  rasping  cry  which  is  very  suggestive.  Edema  of  the 
glottis  due  to  laryngitis  may  cause  marked  dyspnea,  while  death 
may  result  from  sudden  spasm  of  the  glottis.  The  process  may  be 
so  severe  as  to  cause  ulceration  and  upon  healing  leave  cicatrices 
which  later  may  break  down.     Late  in  the  course  of  congenital 


SYPHILIS  OF  THE  GASTRO-INTESTINAL   TRACT         383 

syphilis  the  larynx  may  be  the  seat  of  gummata  which  will  cause 
symptoms  resembling  those  of  similar  conditions  in  the  acquired 
form  of  the  disease. 

Trachea  and  Bronchi. — Conner/  in  a  review  of  128  cases  of  syphilis 
of  the  trachea  and  bronchi,  found  10  cases  in  the  congenital  type  of 
the  disease.  The  lesions  differed  in  no  respect  from  those  found  in 
acquired  syphilis.     The  symptoms  produced  are  also  similar. 

Lungs. — The  most  characteristic  condition  in  the  lungs  in 
congenital  syphilis  is  the  so-called  white  pneumonia  of  Virchow, 
which  consists  of  an  increase  in  the  size  of  the  lung,  the  surface  of 
which  when  cut  is  whitish,  grayish  or  of  a  mottled  red  and  gray 
appearance.  Microscopically,  there  is  thickening  of  the  alveolar 
walls  and  an  infiltration  of  the  alveoli  and  smaller  bronchi  with 
inflammatory  and  epithelial  cells,  many  showing  fatty  degenera- 
tion. Treponemata  are  found  usually  in  large  numbers  along  the 
walls  of  the  capillaries  and  alveoli  and  sometimes  within  the  inflam- 
matory cells  filling  the  alveoli.  One  or  both  lungs  may  be  affected 
or  perhaps  only  one  lobe  of  one  lung. 

A  more  advanced  stage  of  this  type  of  pneumonia  is  more  of  an 
interstitial  form.  The  lung  is  harder  and  tougher  than  normal. 
A  round-cell  infiltration  of  the  intra-alveolar  connective  tissue  is 
noted  microscopically  and  there  is  increase  in  the  number  of  small 
bloodvessels. 

Gummata  of  the  lung  are  rare  in  congenital  syphilis  but  when 
found  differ  in  no  respect  from  gummata  in  the  acquired  form. 

Most  authorities  state  that  involvement  of  the  lung  in  congenital 
syphilis  cannot  be  recognized  during  life,  or  at  least  that  on  account 
of  the  fact  that  these  conditions  so  commonly  are  fatal  they  may  be 
said  to  have  no  clinical  manifestations. 

Still,^  however,  cites  several  cases  which  lived  a  year  or  more  and 
states  that  the  condition  is  easily  recognized,  clinically,  by  the  con- 
traction of  one  side  of  the  thorax,  signs  of  consolidation,  bron- 
chiectasis and  displacement  of  the  heart  toward  the  affected  side. 

SYPHILIS    OF   THE   GASTRO-INTESTINAL   TRACT. 

Mouth. — The  syphilomycodermata  occurring  in  the  mouth  have 
been  described  above.  When  ulcerating  gummata  occur  on  the 
soft  or  hard  palate  perforation  or  even  more  serious  deformity 
may  occur. 

Teeth. — Congenital  syphilis  may  affect  the  teeth  in  two  ways, 
namely,  by  retarded  eruption  and  by  malformation.  The  milk 
teeth,  as  a  rule,  are  not  affected  in  congenital  syphilis,  although 

1  Am.  Jour.  Med.  Sc,  1903,  cxxxvi,  p.  57. 

^  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  i,  p.  297. 


384 


REGIONAL  SYPHILIS 


they  may  decay  earlier  and  more  frequently  than  those  of  normal 
individuals. 

The  permanent  teeth,  however,  may  show  very  striking  abnor- 
malities. These  abnormalities  may  consist  of  almost  any  malfor- 
mation in  size,  shape  and  position  and  are  due  to  the  influence  of 
syphilis  during  the  course  of  the  development  of  the  teeth.  The 
most  typical  of  these  malformations  are  the  so-called  Hutchinson's 
teeth,  first  described  by  Sir  Jonathan  Hutchinson'^  in  1861.  In 
such  teeth  there  is  a  decided  crescentic  notching  of  the  free  border, 
the  lateral  angles  are  rounded,  and  the  tooth  tapers  from  above 
downward  (peg-shaped) .  The  condition  usually  is  symmetrical  and 
the  teeth  most  frequently  affected  are  the  upper  central  incisors, 
although  the  other  incisors  occasionally  are  involved.  Rarely  one 
tooth  alone  is  affected.  When  the  teeth  first  erupt  the  free  border 
does  not  possess  the  crescentic  shape  but  presents  a  rough  saw-like 
edge  which  gradually  wears  away,  leaving  the  typical  notch.  As 
the  child  grows  older  this  in  turn  is  worn  away  and  the  edge  becomes 
more  or  less  straight. 


Fig.  75. — Hutchinson's  teeth  in  congenital  syphilis. 

Other  abnormalities  of  the  teeth  consist  of  transverse  furrows 
of  the  incisors,  widely  separated  teeth,  micodentism,  changes  in 
type,  for  example,  canines  resembling  incisors,  and  early  and  fre- 
quent decay.  Not  infrequently  two  or  more  types  of  abnormality 
may  be  present  in  one  person. 

Hutchinson  considered  the  type  of  deformity  bearing  his  name 
to  be  pathognomonic  of  congenital  syphilis,  but  such  is  not  the  case, 
as  typical  Hutchinson  teeth  occasionally  are  seen  in  other  condi- 
tions where  syphilis  is  absent.  Any  severe  disease  occurring  before 
the  eruption  of  the  permanent  teeth  may  cause  these  deformities, 
and  on  the  other  hand,  the  teeth  of  many  congenital  syphilitics 
do  not  show  such  changes. 

Esophagus,  Stomach  and  Intestines. — Most  syphilographers  have 
paid  scant  attention  to  affections  of  these  portions  of  the  gastro- 
intestinal tract  in  congenital  syphilis.    Peyer's  patches  are  occasion- 


i  Brit.  Med.  Jour.,  1861,  p.  515. 


SYPHILIS  OF  THE  GASTRO-INTESTINAL   TRACT         385 

ally  the  seat  of  the  syphilitic  process  and  the  term  syphilis  annularis 
intestini  has  been  applied,  while  Parrot^  is  said  to  have  described 
gummatous  infiltration  and  ulceration  of  Peyer's  patches. 

No  description  of  the  clinical  manifestations  of  syphilis  of  these 
portions  of  the  alimentary  tract  in  congenital  is  available,  but 
should  such  conditions  be  present  they  undoubtedly  would  present 
symptoms  in  every  way  comparable  to  the  symptoms  produced  by 
involvement  of  these  regions  in  the  acquired  type  of  the  disease. 
In  fact,  it  is  well  known  that  intestinal  disturbances  are  quite 
frequent  in  congenital  syphilis  and  it  is  well  within  the  range  of 
possibility  that  these  may  be  due,  partially  at  least,  to  lesions  of 
these  regions. 

Liver. — The  liver  is  one  of  the  most  frequently  affected  organs 
in  the  body  in  congenital  syphilis.  In  fact,  this  organ  is  found  almost 
constantly  involved  in  stillborn  syphilitic  infants.  The  reason  for 
this  undoubtedly  is  that  it  receives  maternal  blood  direct  by  the 
umbilical  vein.  The  liver  usually  is  enlarged  and  hard  with  rounded 
edges.  On  section  it  is  of  a  light  yellow  color,  usually  with  many 
opaque  white  spots,  which  upon  microscopic  examination  are  found 
to  be  miliary  gummata.  There  is  a  slight  inflammatory  exudation 
and  marked  proliferation  of  the  connective-tissue  cells  due  to  the 
presence  of  the  treponemata.  The  proliferation  is  due  to  efforts 
at  regeneration  and  the  connective  tissue  is  most  abundant  where 
the  treponemata  are  most  numerous.  The  contraction  of  the 
collagen  fibrils  causes  compression  of  the  liver  cells  which  results 
in  atrophy.  This  condition  occurring  in  utero  may  be  followed  by 
hydramnios  due  to  obstruction  of  umbilical  vein. 

In  syphilitic  involvement  of  the  liver  in  late  congenital  syphilis 
the  condition  may  resemble  syphilitic  cirrhosis  in  the  acquired  form. 
Perihepatitis  and  gummata  also  rarely  are  found. 

Quite  marked  involvement  of  this  organ  by  the  Treponema 
pallidum  in  congenital  syphilis  may  be  present  without  demon- 
strable symptoms.  However,  in  a  considerable  percentage  of  cases 
enlargement  may  be  detected.  In  the  majority  of  instances  this  is 
slight  but  the  liver  may  reach  quite  a  large  size  and  be  distinctly 
palpable.  Ascites  does  not  occur  in  the  early  involvement  of  the 
liver  in  congenital  syphilis,  but  later  in  the  course  of  the  disease 
a  typical  syphilitic  cirrhosis  with  acites  may  occur  with  other  symp- 
toms as  in  the  acquired  form. 

Jaundice  also  is  exceedingly  rare  in  early  involvement  of  the 
liver  in  congenital  syphilis.  The  symptoms  associated  with  gum- 
mata of  the  liver  differ  in  no  respect  from  those  observed  with 
gummata  in  the  acquired  form  of  syphilis. 

1  Cited  by  Marshall:  Syphilology  and  Venereal  Disease,  New  York,  1906,  pi  360. 
25 


386  REGIONAL  SYPHILIS 

Gall-bladder. — ^The  only  reference  to  syphilis  of  the  gall-bladder 
found  in  the  literature  is  the  case  of  Beck^  in  which  the  gall-bladder 
of  an  eight-months-old  fetus  was  found  affected. 

Spleen. — The  spleen  qtiite  frequently  is  involved  in  early  cases 
of  congenital  syphilis,  and  less  often  in  the  late  cases.  The  usual 
condition  is  a  slight  enlargement  due  to  round-cell  infiltration  and 
proliferation  of  the  connective-tissue  elements.  The  enlargement, 
however,  may  be  marked  so  that  the  organ  is  distinctly  palpable 
while  tenderness  may  or  may  not  be  present.  Numerous  trepone- 
mata  generally  are  found,  especially  in  the  walls  of  the  arteries. 
Gummata  of  the  spleen  and  amyloid  degeneration  also  have  been 
described  in  congenital  syphilis. 

Pancreas. ^ — This  organ  rarely  is  affected  in  congenital  syphilis, 
though  perhaps  more  often  than  it  is  in  the  acquired  form  of  the 
disease.  The  usual  condition  is  a  diffuse  interstitial  fibrosis.  As 
far  as  the  author  is  aware  the  Treponema  pallidum  has  not  been 
demonstrated  in  the  pancreas  of  congenital  syphilitics. 

While  affections  of  the  pancreas  rarely  may  be  found  postmortem 
in  congenital  syphilis,  no  symptoms  have  been  described  during  life 
referable  to  this  organ. 

Marshall  has  suggested  that  syphilis  of  the  pancreas  may  be  the 
cause  of  diabetes  occurring  in  children  and  adolescents. 

THE   THYROID    GLAND. 

Involvement  of  the  thyroid  in  congenital  syphilis  is  exceedingly 
rare.  Davis^  quotes  Demme  as  having  observed  children  with  gum- 
matous nodules  in  the  thyroid,  and  Furst  as  having  observed  the 
case  of  a  child  born  with  a  goitre  of  considerable  size,  which  he 
thought  was  undoubtedly  due  to  syphilis. 

Congenital  syphilis  of  the  thyroid  may  produce  marked  symp- 
toms of  exophthalmic  goitre,  as  in  a  case  reported  by  Clark^  in  which 
symptoms  developed  twenty-four  years  after  birth.  A  positive 
Wassermann  reaction  was  obtained  in  this  case  as  well  as  in  the 
mother  of  the  patient  and  the  symptoms  disappeared  under  specific 
therapy. 

THE   THYMUS    GLAND. 

Syphilis  of  the  thymus  also  is  rare,  but  according  to  Adami^ 
gummata   and   diffuse   fibroid    induration    have    been    observed. 

1  Prag.  med.  Wchnschr.,  1884,  ix,  p.  257. 

'^  Syphilology  and  Venereal  Disease,  New  York,  1906,  p.  359. 

3  Arch.  Int.  Med.,  1910,  v,  p.  47. 

4  Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  p.  1951. 

6  Pathology,  Philadelphia  and  New  York,  1911,  p.  732. 


THE  GENITO-URINARY  ORGANS  387 

Hocksinger"^  states  that  the  thymus  may  be  so  enlarged  as  to  pro- 
duce stenosis  of  the  trachea  with  stridor  thymicus,  but  that  the 
enlargement  disappears  under  specific  therapy. 

THE   ADRENALS. 

After  the  liver  and  spleen  the  adrenals  seem  to  be  the  organs 
most  frequently  involved  in  congenital  syphilis.  Symptoms  refer- 
able to  such  involvement  have  not  been  described.  It  may  be, 
however,  that  certain  cases  of  Addison's  disease  are  due  to  con- 
genital syphilis  of  the  adrenals. 

THE    GENITO-URINARY   ORGANS. 

Testicles. — Syphilitic  orchitis  is  not  infrequent  in  congenital 
syphilis.  It  is  most  often  found  during  infancy  but  has  been 
observed  in  children  and  even  in  adult  life.  It  usually  is  bilateral 
but  may  be  unilateral.  The  epididymis  rarely  is  involved  and  hydro- 
cele is  uncommon.  The  condition  usually  is  a  diffuse  inflammatory 
process,  although  gummata  have  been  observed.  Rarely  the  devel- 
opment of  the  testicles  is  arrested  in  utero,  and  infantilism  results, 
the  testicles  being  small  and,  as  a  rule,  functionless.  In  syphilitic 
orchitis  the  testicle  is  enlarged,  hard  and  sometimes  tender,  while 
gummata  of  the  testicle  may  rarely  break  down  and  ulcerate. 

Uterus  and  Ovaries. — Actual  involvement  of  the  uterus  in  con- 
genital syphilis  has  not  been  observed  as  far  as  the  author  is 
aware,  however,  certain  congenital  abnormalities,  such  as  uterus 
bicornis,  etc.,  may  indirectly  be  due  to  syphilis.  That  the  ovaries 
of  congenital  syphilitics  may  be  affected  with  syphilis  is  proven  by 
the  finding  of  the  treponemata  in  these  organs  in  a  child  of  one 
year,  by  Levaditi  and  Sauvage,^  and  in  a  fetus  of  seven  months  by 
Hoffman  and  Wolters.^  However,  no  symptoms  referable  to  involve- 
ment of  these  organs  in  congenital  syphilis  have  been  described. 

Kidney. — Syphilitic  nephritis,  both  acute  and  chronic,  has  been 
observed  in  congenital  syphilis,  and  may  occur  at  nearly  any  age. 
The  condition  usually  is  interstitial,  although  it  may  be  parenchy- 
matous. During  the  active  eruptive  stage  in  infants  acute  neph- 
ritis is  not  infrequent,  although  it  clears  up  quite  readily  under 
specific  therapy.  Treponemata  have  frequently  been  demonstrated 
in  large  numbers  in  the  connective-tissue  stroma  of  the  kidney  and 

1  Pfaundler  and  Schlossmann:  Diseases  of  Children,  Philadelphia  and  London, 
1912,  p.  553. 

2  Cited  by  Metchinkoff  in  Power  and  Murphy's  System  of  Syphilis,  London,  1908, 
i,  p.  64. 

3  Ibid. 


REGIONAL  SYPHILIS 

in  less  numbers  in  the  tubules  and  between  the  epithelial  cells. 
Gummata  of  the  kidney  have  not  been  observed  in  congenital 
syphilis. 

THE   BONES. 

Involvement  of  the  bones  is  quite  frequent  in  congenital  syphilis, 
and  those  bones  which  are  preformed  in  cartilage  are  more  often 
affected  before  birth,  while  those  bones  which  are  formed  in  mem- 
brane are  attacked  after  birth.  It  seems  that  the  syphilitic  process 
is  more  prone  to  invade  those  portions  of  the  bones  in  which  growth 
is  most  active.  It  is,  therefore,  that  the  so-called  osteochondritis 
of  Wegner  is  the  most  frequent  pathological  process  in  the  bones 
of  congenital  syphilitics.  This  lesion  is  found  along  the  border 
zone  between  the  epiphysis  and  diaphysis  of  the  long  bones,  and 
is  often  erroneously  termed  epiphysitis.  Normally  in  ossification  in 
the  long  bones  the  border-line  between  the  zones  of  calcification  and 
ossification  is  straight  or  slightly  curved,  narrow  and  sharply 
defined.  In  the  syphilitic  lesion  the  border-line  is  broader  and 
irregular.  Various  grades  of  severity  of  the  process  are  observed. 
If  the  lesion  be  of  moderate  degree,  a  white  or  reddish-white  zone, 
about  2  mm.  in  width,  is  seen  between  the  cartilage  and  the  new- 
formed  spongy  bone.  This  consists  of  calcified  cartilage  in  which 
the  rows  of  cartilage  cells  are  more  numerous  than  normal.  When 
the  lesion  is  more  pronounced  the  zone  of  calcification  is  broader, 
more  irregular  and  less  sharply  outlined  against  the  zone  of  ossifi- 
cation. It  also  contains  a  greater  number  of  cartilage  cells  than 
normal.  The  cartilage  next  to  the  zone  of  calcification  is  softer, 
contains  numerous  bloodvessels  and  sometimes  small  zones  of  con- 
nective-tissue calcification  or  irregular  ossification.  If  the  process 
is  most  severe  the  periosteum  and  perichondrium  are  thickened 
and  the  bone  is  found  pouched  out  at  the  sides  around  the  zones 
of  calcification  and  ossification.  The  zone  of  calcification  is  white, 
irregular,  hard  and  friable.  This  is  mainly  made  up  of  irregular 
rows  of  degenerated  and  distorted  cartilage  cells  which  are  surrounded 
by  a  calcified  substance  consisting  of  irregular  masses  of  atypical 
bone  tissue  and  bloodvessels  which  in  turn  are  surrounded  by 
cells  of  various  shapes.  Between  this  zone  of  calcification  and  the 
new-formed  bone  a  grayish  or  grayish-yellow  zone,  irregular  and 
from  2  to  4  mm.  in  thickness  is  seen.  This  is  made  up  of  vascular 
tissue,  round  and  spindle-shaped  cells  and  a  homogeneous  sub- 
stance, and  forms  a  loose,  easily  detached  connection  between  the 
diaphysis  and  the  cartilage. 

Not  infrequently  different  degrees  of  severity  of  the  process  are 
observed  in  the  same  individual.  The  most  severe  degree  is  found  in 
the  lower  end  of  the  femur,  after  which  the  lower  ends  of  the  tibia 


THE  BONES  389 

and  fibula,  the  ulna  and  radius,  the  upper  ends  of  the  tibia,  femur 
and  ulna  are  affected  most  severely. 

The  early  or  mild  degrees  of  the  osteochondritis,  as  a  rule,  cannot 
be  recognized  macroscopic-ally  but  are  revealed  by  the  microscope. 
The  more  severe  processes  are  also  revealed  by  the  x-rays. 

Clinically,  the  osteochondritis  if  of  a  mild  degree  cannot  be  recog- 
nized. However,  if  the  process  is  severe  a  swelling  of  the  bone 
with  more  or  less  tenderness  in  the  region  of  the  epiphysis  may  be 
detected  and  the  so-called  pseudoparalysis  of  Parrot  observed. 
This  apparent  paralysis  is  due  to  the  pain.  The  condition  usually 
is  seen  during  the  first  three  months,  often  very  early  and  never 
later  than  the  sixth  month.  It  is  observed,  according  to  various 
authors  in  from  11  to  25  per  cent,  of  cases. 

Later  in  the  course  of  congenital  syphilis  a  periostitis  or  osteitis 
may  be  noted  and  may  occur  in  the  long  bones  or  in  the  bones  of 
the  face  or  skull.  It  may  be  a  diffuse  process  and  involve  nearly 
the  entire  diaphysis  or  it  may  be  noted  in  circumscribed  areas. 
It  usually  starts  in  the  solid  bone  and  grows  outward  to  the  perios- 
teum and  inward  to  the  medulla.  When  the  process  breaks  through 
the  periosteum  the  soft  tissues  become  involved  and  sinuses  are 
formed.  The  affected  bone  is  more  or  less  changed  in  size  and  shape 
and  nodides  or  exostoses  may  develop. 

Periostitis  and  osteitis  will  cause  s\TQptoms  depending  upon  the 
bone  affected  and  the  extent  of  the  process.  Pain,  severe  and  per- 
sistent, especially  at  night,  may  be  noticed. 

Probably  the  most  frequently  involved  bone  in  congenital  sj'philis 
is  the  tibia  and  when  this  bone  is  typically  affected  it  constitutes 
an  almost  pathognomonic  sign.  The  middle  third  of  the  diaphysis 
most  often  is  involved,  although  the  process  may  extend  through- 
out the  entire  length  of  the  bone.  There  is  thickening,  especially 
anteroposteriorly,  giving  the  bone  an  appearance  of  being  bent, 
the  so-called  "saber  tibia."  Subjective  s\Tnptoms,  as  a  rule,  are 
slight  or  absent,  although  nocturnal  pain  and  aching  and  some 
tenderness  are  occasionally  complained  of. 

The  bones  of  the  skull  may  be  attacked  and  more  or  less  deformity 
result. 

The  so-called  Parrot's  nodes  are  protuberances  or  bosses  due  to 
diffuse  periostitis.  If  the  frontal  bone  alone  is  affected,  the  "OhTn- 
pian  brow"  will  result,  while  if  the  parietal  bones  are  affected  as 
well,  the  " hot-cross-bun"  deformity  will  exist.  Craniotabes  which 
consists  of  a  thinning  of  the  bones  of  the  skull,  is  not  a  rare  condition. 
It  is  due  to  pressure  on  the  bone  during  development. 

Both  of  these  affections  have  been  ascribed  to  rickets  and 
undoubtedly  do  occur  in  this  condition  but  probably  more  fre- 
quently when  associated  with    congenital    syphilis.      As   a  rule 


390  REGIONAL  SYPHILIS 

Parrot's  nodes  and  craniotabes  are  early  manifestations  of  the 
disease  occurring  within  a  few  weeks  to  a  few  months  after  birth. 

Various  cranial  deformities,  saddle-nose,  perforated  palate,  etc., 
and  of  the  pelvis  may  be  the  result  of  osteitis  and  periostitis. 

Gummata  of  the  bone  which  is  a  very  rare  condition  in  con- 
genital syphilis  will  cause  symptoms  and  results  depending  upon 
the  bone  or  bones  affected,  and  they  differ  in  no  respect  from  those 
of  gummata  in  acquired  syphilis. 

Dactylitis  is  unusual  in  congenital  syphilis.  It  occurs,  as  a  rule, 
during  the  first  year  and  is  exceedingly  rare  after  the  second  year. 
The  fingers  are  affected  more  frequently  than  the  toes  and  occa- 
sionally the  metacarpal  bones  are  involved.  The  symptoms  do 
not  differ  from  those  found  in  dactylitis  of  acquired  syphilis. 

Graves^  has  called  attention  to  the  frequent  occurrence  of  the 
so-called  scaphoid  scapula  in  children  of  syphilitic  parents,  although 
also  found  when  no  syphilis  exists.  The  chief  characteristic  of  this 
condition  is  that  the  vertebral  border  below  the  spine  of  the  scapula 
is  concave  instead  of  showing  the  normal  convexity. 

THE   JOINTS. 

Simple  arthralgia  in  which  no  demonstrable  lesion  exists  is  seen 
in  congenital  syphilis  as  well  as  in  the  acquired  type.  It  occurs, 
as  a  rule,  early  in  the  course  of  the  disease  and  differs  in  no  respect 
from  that  of  acquired  syphilis. 

Chronic  synovitis  with  effusion  and  osteo-arthritis  due  to  hyperos- 
tosis are  of  not  infrequent  occurrence  and  are  characterized  by  their  , 
slow  development,  chronic  course,  absence  of  pain,  and  slight 
limitation  of  movement.  These  conditions  are  of  the  later  mani- 
festations of  congenital  syphilis  occurring,  as  a  rule,  between  the 
fifth  and  fifteenth  years. 

The  so-called  syphilitic  arthritis  deformans  of  Fournier  which  is 
produced  by  osteophytic  outgrowths  from  the  epiphyses  is  charac- 
terized by  the  limitation  of  movement  and  even  ankylosis,  while 
more  or  less  wasting  of  the  muscles  may  occur.  The  usual  date  of 
the  appearance  of  this  type  of  arthropathy  is  between  the  fifth  and 
twelfth  years.  The  symptoms  of  Charcot's  joint  may  occur  in 
juvenile  tabes  and  differ  in  no  respect  from  the  same  condition  in 
tabes  due  to  acquired  syphilis. 

THE  BURS.ffi. 

From  the  scanty  literature  on  the  subject  it  would  seem  that 
syphilitic  bursitis  is  exceedingly  rare  in  the  congenital  form  of  the 

1  Recent  Studies  in  Syphilis,  St.  Louis,  1911,  p.  118. 


THE  TENDONS  AND  MUSCLES  391 

disease.  It  is  possible,  however,  that  some  of  the  cases  reported 
as  specific  arthritis  are  in  reaUty  bursitis  or  at  least  that  the  bursse 
as  well  as  the  joints  are  affected. 

The  only  case  of  which  the  author  is  able  to  find  record  was 
reported  by  Coues^  in  1915.  This  case  was  a  boy  of  thirteen 
years,  who  had  always  had  "something  the  matter."  Two  months 
previous  to  being  examined  he  had  had  trouble  with  his  right  elbow 
followng  a  fall.  There  was  considerable  swelling  and  disability 
which  persisted  for  a  time,  then  partially  disappeared  but  again 
became  worse  until  another  fall  occurred  the  day  before.  Follow- 
ing this  there  was  a  great  deal  of  pain  and  disability. 

The  examination  showed  a  fairly  well-nourished  and  developed 
boy,  although  rather  undersized.  There  were  no  obvious  signs  of 
congenital  syphilis.  The  right  elbow  was  swollen,  especially  over 
the  olecranon,  while  there  was  some  tenderness  over  the  external 
condyle.  Motion  was  limited  and  painful.  At  a  later  examination 
two  small  pieces  of  bone  were  felt  through  the  fluid  of  the  olecranon 
bursa.  Owing  to  the  tenderness  in  the  region  of  the  external  condyle 
it  was  supposed  that  there  was  a  separation  of  the  epiphysis  or  a 
fracture.  The  a;-rays,  however,  showed  that  the  joint  was  normal. 
After  five  weeks  as  there  was  no  improvement  an  operation  was 
decided  upon.  At  this  time  it  was  determined  that  cardiac  dilata- 
tion and  mitral  insufficiency  existed  and  a  probable  diagnosis  of 
specific  myocarditis  was  made.  It  was  also  determined  that  the 
shin  bones  were  tender  to  pressure  and  the  .r-rays  revealed  slight 
but  definite  periostitis  of  the  tibia.  The  Wassermann  test  was 
negative. 

The  bursse  of  the  right  elbow  were  opened  under  cocaine  and  a 
gummy,  honey-like  material  was  evacuated  with  a  small  amount 
of  pus.  Two  small  worm-eaten  pieces  of  bone  were  removed  from 
the  cavity  which  did  not  connect  with  the  joint.  No  microscopic 
examinations  were  made.  Under  specific  therapy  the  elbow  returned 
to  normal  and  the  heart  condition  improved. 


THE   TENDONS    AND  MUSCLES. 

The  author  has  been  unable  to  find  any  reference  in  the  litera- 
ture to  involvement  of  the  tendons  and  muscles  in  congenital 
syphilis  with  the  exception  of  one  case  of  gumma  of  the  gastroc- 
nemius and  four  cases  of  gumma  of  the  muscles  of  the  tongue 
reported  by  Fournier.^ 

1  Boston  Med.  and  Surg.  Jour.,  1915,  clxxiii,  p.  18. 

2  Cited  by  Hartley  in  Morrow's  System,  of  Genito-urinary  Diseases,  Syphilology 
and  Dermatology,  New  York,  1898,  ii,  p.  261. 


392  REGIONAL  SYPHILIS 

THE   NERVOUS   SYSTEM. 

Jonathan  Hutchinson/  even  so  late  as  1899,  wrote  that  there 
was  good  reason  to  beUeve  that  involvement  of  the  nervous  system 
was  very  infrequent  in  congenital  syphilis,  and  that  it  never 
occurred  to  him  in  a  single  instance  to  identify  congenital  syphilis 
with  sufferers  from  tabes  and  general  paralysis. 

Since  that  time  abundant  evidence  has  been  brought  forth 
proving  the  affection  of  the  nervous  system  in  congenital  syphilis. 
Rumpf^  states  that  in  13  per  cent,  of  all  cases  of  hereditary  syphilis 
there  is  involvement  of  the  nervous  system. 

All  types  of  syphilis  of  the  nervous  system  found  in  the  acquired 
form  may  be  seen  in  congenital  syphilis,  including  arteritis,  men- 
ingitis, syphilis  of  the  brain  substance  (gummata  and  paresis), 
syphilis  of  the  cord  substance  (gummata  and  tabes)  and  syphilis  of 
the  nerves.    As  a  rule,  however,  various  lesions  are  combined. 

Treponemata  have  been  found  in  the  meninges  and  walls  of  the 
bloodvessels  of  the  brain  in  congenital  syphilis  by  numerous  investi- 
gators, but  as  far  as  the  author  is  aware  these  organisms  have  not 
been  demonstrated  in  the  brains  of  juvenile  paretics  or  the  cords 
of  juvenile  tabetics. 

Certain  malformations  of  the  nervous  system  not  seen  in  the 
acquired  type  of  syphilis  are  observed  in  the  congenital  form.  One 
of  the  most  frequent  of  these  is  hydrocephalus.  This  condition  is 
produced  by  an  accumulation  of  fluid  in  the  lateral  ventricles  and 
may  be  due  to  any  condition  which  prevents  the  escape  of  the  fluid 
and  therefore  is  found  in  other  conditions  than  syphilis. 

As  pointed  out  above,  certain  abnormal  infants  sometimes  are 
produced  as  the  product  of  conception  when  one  or  both  of  the 
parents  are  syphilitic  without  actual  infection  of  the  fetus  with  the 
Treponema  pallidum.  Monsters  of  various  types,  especially  those 
with  gross  abnormalities  of  the  brain,  and  individuals  with  defec- 
tive mental  development,  morons,  imbeciles,  and  idiots  not  infre- 
quently are  observed.  These  abnormal  infants  also  are  found 
with  positive  evidences  of  syphilis. 

Involvement  of  the  nervous  system  may  occur  in  utero  and  still- 
birth follow  or  a  living  child  may  be  born  with  manifestations  of 
nervous-sytem  involvement  present  or  such  manifestations  may 
develop  at  almost  any  subsequent  time. 

As  stated  above,  all  of  the  lesions  of  acquired  syphilis  of  the 
nervous  system  are  found  in  the  congenital  form  of  the  disease,  and 

1  Steadman:  Twentieth  Century  Practice  of  Medicine,  New  York,  1899,  xviii, 
p.  394. 

2  Cited  by  Nonne:  Syphilis  and  the  Nervous  System,  Philadelphia  and  London, 
1913,  p.  313. 


THE  NERVOUS  SYSTEM  393 

even  more  frequently  than  in  the  former  are  two  or  more  types  of 
pathological  picture  observed.  For  example,  an  arteritis  and  a 
meningitis  usually  are  associated.  This  is  especially  true  of  early 
involvement  of  the  nervous  system.  It  is  therefore  to  be  expected 
that  the  clinical  course  will  present  a  mixed  picture  with  varied 
and  complex  findings.  However,  the  same  symptoms  as  are 
observed  in  acquired  syphilis  are  found  in  the  congenital  type, 
hemiplegias,  paraplegias,  reflex  disturbances,  headache,  mental 
derangements,  etc.,  although  modified  to  a  greater  or  lesser  extent. 

Symptoms  depending  upon  conditions  not  found  in  acquired 
syphilis  also  are  observed. 

One  of  the  most  frequent  of  the  early  manifestations  of  involve- 
ment of  the  nervous  system  in  congenital  syphilis  which  is  not 
seen  in  the  acquired  form  is  hydrocephalus.  This  condition  may  be 
observed  at  birth  or  it  may  not  develop  till  puberty,  however,  the 
most  frequent  time  of  its  appearance  is  when  the  child  is  between 
three  and  eleven  months  of  age.  Occasionally  clinical  symptoms 
are  absent,  but,  as  a  rule,  there  is  irritability,  sleeplessness,  kicking, 
screaming  and  movements  of  the  hands  and  arms.  Vomiting  is 
not  rare  and  retraction  of  the  head  often  is  observed.  Nystagmus 
and  irregular  and  fixed  pupils  are  frequent.  Spasticity  and  rigidity 
sometimes  are  present.  The  temperature  is  normal  or  only  slightly 
raised. 

While  juvenile  paresis  and  juvenile  tabes  are  similar  to  the  same 
conditions  observed  in  acquired  syphilis  they  deserve  special 
mention. 

Juvenile  Paresis. — According  to  Kraepelin,^  the  first  case  of 
juvenile  paresis  to  be  described  was  reported  in  1877  by  Clouston, 
since  which  time  numerous  cases  have  been  observed.  In  the  past 
year  the  author  has  seen  two  cases.  Symptoms  of  the  disease  may 
begin  as  early  as  the  fifth  or  sixth  year,  although,  as  a  rule,  the 
onset  is  somewhat  later  (seventh  to  twelfth  year). 

Paresis  due  to  congenital  infection  must  now  be  regarded  either 
as  a  recurrence  or  as  a  case  of  syphilis  hereditaria  tarde,  as  it  has 
been  noted  following  early  manifestations  of  congenital  syphilis 
and  also  when  such  symptoms  were  absent  or  overlooked. 

The  child  may  or  may  not  have  appeared  normal  up  to  the  time 
of  the  development  of  paretic  symptoms,  although,  as  a  rule, 
there  is  a  history  of  backwardness,  both  in  physical  and  mental 
development. 

The  clinical  picture  usually  is  one  of  dementia  and  formerly 
many  cases  undoubtedly  were  diagnosed  as  idiocy  or  imbecility, 
although   as   Kraepelin^    states,  childish  ideas   of   grandeur  may 

1  General  Paresis,  New  York,  1913,  p.  145.  2  ibid. 


394 


REGIONAL  SYPHILIS 


occur.  Convulsions  usually  of  an  epileptiform  character  are  very 
frequent  in  juvenile  paresis,  often  occurring  daily  or  even  many 
times  daily. 

The  course  of  this  malady  is,  as  a  rule,  protracted,  lasting  some- 
times, as  in  Kraepelin's^  case,  as  long  as  nine  years. 

The  following  case  observed  by  the  author  is  quite  typical: 

H.  J.,  male,  aged  sixteen.    (See  Fig.  76.) 

Family  History. — Mother  died  at  age  of  thirty-six,  cause  unknown. 
Not  known  if  father  is  living.  One  sister,  aged  twenty-five,  living 
and  married,  but  has  no  children.  One  sister  died  at  age  of  two 
months,  cause  unknown.  Twin  brothers  alive  and  said  to  be  well 
at  age  of  thirteen. 


Fig.  76. — Juvenile  paretic  showing  slight  notching  of  upper  central  incisors 


Personal  History. — Patient  said  to  have  been  nervous  in  school 
and  did  not  learn  rapidly.  No  history  of  diseases  in  childhood,  and 
is  said  to  have  been  well  until  four  years  ago  when  "eyes  began 
troubling  him." 

Present  illness  began  about  one  year  ago  with  extreme  nervousness 
and  loss  of  vision  in  left  eye.  Later  he  suffered  with  fainting  spells 
followed  by  aphonia. 

In  October,  1914,  the  patient  received  inunctions  of  mercury 
with  improvement.  Later,  nervousness  increased,  with  loss  of 
memory,  irritability  and  fits  of  uncontrollable  temper. 

Examination. — April  10,  1915.  Boy,  apparently  fifteen  or  six- 
teen years  of  age  is  well  nourished,  muscles  are  firm,  but  asthenic. 


1  General  paresis,  New  York,  1913,  p.  145. 


THE  NERVOUS  SYSTEM 


395 


Facial  expression  is  dull  and  expressionless.  Heart,  lungs  and 
abdominal  viscera  apparently  are  normal.  No  luetic  scars  or  aden- 
itis is  present.  Upper  central  incisors  are  slightly  notched.  There 
is  slight  convergent  strabismus  in  left  eye;  nystagmus  in  both  eyes. 
Both  pupils  irregular  in  outline  and  do  not  react  to  light.  Left 
pupil  reacts  to  accommodation.  Upper  tendon  reflexes  are  normal. 
Lower  tendon  reflexes  are  markedly  exaggerated.  Ankle-clonus 
and  Romberg  sign  are  positive.  Coarse  tremor  of  hands  and  fingers 
and  fibrillary  tremor  of  tongue  are  noticed. 


Fig.  77. — Juvenile  paresis  in  the  emaciated  stage.     (Jelliffe  and  White.) 


Speech  is  slow  and  hesitating  and  articulation  poor.  Memory 
both  for  recent  and  remote  events  is  poor.  Fund  of  acquired 
knowledge  is  slight.  Orientation  for  place  and  personality  is  not 
impaired.  He  could  not  tell  the  day  of  the  week,  although  he  said 
it  was  springtime. 

Laboratory  Findings. — Wassermann  on  blood  +  +  H — h  •  Was- 
sermann  on  spinal  fluid  -\ — h  +  +•     Lymphocytes,  16  per  c.mm. 


396  REGIONAL  SYPHILIS 

Globulin  H — |-.  Colloidal  gold  test,  typical  paretic  curve.  Luetin 
test  negative. 

The  patient  was  treated  with  mercury  inunctions  until  slightly 
salivated  and  large  doses  of  potassium  iodide  were  administered. 
Intraspinal  medication  was  refused  and  no  further  treatment  was 
employed.  The  patient  left  Hot  Springs  in  July,  1915,  apparently 
in  the  same  condition  as  when  first  seen. 

Juvenile  tabes  is  a  much  more  rare  condition  than  juvenile  paresis. 
The  date  of  onset,  as  a  rule,  is  earlier  than  in  the  latter  condition, 
the  first  symptoms  usually  being  observed  between  the  fifth  and 
tenth  years,  although  cases  developing  as  late  as  the  twenty-fifth 
year  have  been  reported.  The  symptoms  dififer  but  little  from  those 
observed  in  tabes  following  acquired  syphilitic  infection. 

Mental  Defectives. — Children  of  syphilitic  parents  presenting 
certain  types  of  mental  defect  without  obvious  syphilitic  lesions 
quite  frequently  are  observed.  Some  of  these  show  some  evidence 
of  syphilis,  such  as  interstitial  keratitis,  rhagades,  etc.,  and  a  larger 
number  give  positive  laboratory  evidence.  However,  a  certain 
percentage  of  these  mentally  defective  children,  morons,  imbeciles 
and  idiots,  while  giving  no  evidence  of  actual  infection  with  the 
Treponema  pallidum  undoubtedly  owe  their  unfortunate  condition 
to  the  "sins  of  their  fathers." 

The  diagnosis  of  the  actual  involvement  of  the  nervous  system 
with  the  Treponema  pallidum  in  congenital  syphilis  will  differ  but 
little  from  that  of  acquired  syphilis. 

Hydrocephalus  due  to  syphilis  must  be  differentiated  from  that 
due  to  other  conditions  and  usually  can  be  accomplished  by  the 
finding  of  other  clinical  manifestations  of  syphilis  or  by  positive 
laboratory  evidence. 

The  determination  of  the  role  of  syphilis  in  the  etiology  of  such 
mental  defectives  as  morons,  imbeciles  and  idiots  except  where 
positive  clinical  or  laboratory  findings  of  syphilis  exist  will  depend 
upon  family  evidence.  The  diagnosis  of  the  mental  condition  is 
purely  a  psychiatric  problem  and  is  without  the  scope  of  the 
present  volume. 

THE  EYE. 

The  eye  is  very  frequently  the  seat  of  the  syphilitic  process  in 
the  congenital  type  of  the  disease. 

Iritis  due  to  congenital  syphilis  differs  in  no  respect  from  that 
seen  in  acquired  syphilis,  except,  perhaps,  that  the  process,  as  a 
rule,  is  not  so  severe.  While  usually  developing  during  the  first 
few  months  of  extra-uterine  life  it  may  run  its  entire  course  within 
the  uterus,  the  child  being  born  with  synechia  of  the  iris.  Iritis 
may  also  appear  as  a  symptom  of  syphilis  hereditaria  tarde. 


PLATE   VI 


Interstitial   Keratitis. 


THE  EAR  397 

Cyclitis  almost  invariably  is  an  accompaniment  of  iritis. 

Interstitial  keratitis  is  much  more  frequently  seen  in  congenital 
syphilis  than  in  the  acquired  form.  This  condition  with  Hutchinson 
teeth  and  deafness  without  earache  or  otorrhea  constitutes  the 
so-called  Hutchinson'' s  triad,  which  when  all  are  present  is  practi- 
cally pathognomonic  of  congenital  syphilis. 

Interstitial  keratitis  while  more  frequent  in  the  congenital  form 
of  syphilis  differs  in  no  respect  from  that  seen  in  acquired  syphilis, 
except,  perhaps,  that  in  the  latter  form  of  syphilis  there  is  a  greater 
tendency  for  the  disease  to  remain  unilateral,  while  in  the  former 
type  it  usually  is  bilateral.  Both  eyes,  however,  may  not  be 
affected  simultaneously,  although,  as  a  rule,  they  are  involved  in 
rapid  succession  and  both  corneas  are  opaque  at  the  same  time.  It 
is  most  frequently  seen  between  the  eighth  and  fifteenth  years, 
although  it  has  been  noted  as  early  as  a  few  weeks  after  birth. 

Scleritis  also  is  seen  more  frequently  in  congenital  s\'philis  than 
in  acquired  syphilis  but  presents  no  clinical  differences.  It  is,  as 
a  rule,  a  late  manifestation,  usually  being  observed  after  puberty. 

Choroiditis  and  retinitis  occur  in  the  same  types  in  congenital 
syphilis  as  are  found  in  the  acquired  disease.  They  usually  are 
early  manifestations,  being  seen  most  frequently  diu-ing  the  first 
year. 

Papillitis  as  a  primary  condition  is  rare  in  congenital  s^'philis 
but  more  often  is  seen  as  an  extension  from  the  retina.  It  also  is 
an  early  manifestation  and  the  sjTiiptoms  are  similar  to  those 
observed  in  acquired  syphilis. 

THE  EAR. 

In  early  congenital  s\"philis  not  infrequently  there  is  an  extension 
to  the  middle  ear  of  the  pathological  processes  in  the  nose  and 
pharynx  which  results  in  an  otorrhea. 

Later  in  the  coiu-se  of  the  disease,  usually  between  the  fifteenth 
and  twentieth  years,  a  rapidly  advancing  deafness  may  occur 
which  probably  is  due  to  a  similar  process  to  that  observed  in  the 
internal  ear  in  deafness  due  to  acquired  s^-philis.  There  may  be 
tinnitus  but  usually  the  deafness  is  the  only  s\Tnptom.  Meniere's 
sjTidrome  due  to  congenital  s^'philis  has  also  been  observed. 


CHAPTER    XXIII. 
DIAGNOSIS. 

The  diagnosis  of  congenital  syphilis  depends  upon  the.  history, 
clinical  symptoms  and  laboratory  findings,  of  the  individual  him- 
self and  upon  similar  evidence  in  his  parents  and  brothers  and 
sisters,  although,  as  with  acquired  syphilis,  the  diagnosis,  occasion- 
ally must  rest  on  the  results  of  therapeutic  measures. 

In  the  vast  majority  of  cases  it  is  impossible  to  establish  a  definite 
syphilitic  history  in  the  parents,  especially  in  the  mother,  also  it 
is  comparatively  infrequent  that  active  manifestations  of  the  dis- 
ease are  present  in  the  parents  at  the  time  of  examination  of  the 
patient,  although  when  possible  such  manifestations,  as  well  as  their 
residuals  (scars,  etc.)  should  be  searched  for. 

Of  course  positive  evidence  of  syphilis  in  the  father  with  absolute 
proof  of  its  absence  in  the  mother  would  be  convincing  that  the 
child  was  not  congenitally  syphilitic.  However,  it  may  be  said  that 
absolutely  certain  evidence  of  the  absence  of  syphilis  in  the  mother 
would  be  hard  to  establish. 

The  history  of  conceptions,  both  those  previous  to  the  one 
resulting  in  the  child  under  consideration,  as  well  as  earlier  and 
later  ones  should  also  be  gone  into,  for  with  the  mother  of  syphilitic 
children  the  sequence  of  sterility,  abortions,  stillbirths,  live  chil- 
dren with  syphilitic  manifestations  and  apparently  normal  children 
often  may  be  established.  If  the  mother  shows  any  evidence  of 
congenital  syphilis  herself,  her  family  history  should  also  be  looked 
into.  The  history  of  brothers  and  sisters  should  be  taken  and  they 
should  also  be  examined  carefully  for  evidences  of  the  disease. 

The  Wassermann  test  and  perhaps  the  luetin  should  be  made 
on  all  members  of  the  family,  and  when  iiidicated  the  provocative 
Wassermann  and  lumbar  puncture  with  examination  of  the  spinal 
fluid. 

Of  course  the  establishing  of  syphilis  in  the  mother  or  brothers 
and  sisters  of  an  individual  does  not  of  necessity  mean  that  the 
individual  himself  is  congenitally  syphilitic,  but  in  the  presence  of 
suspicious  symptoms  is  very  strong  presumptive  evidence. 

The  evidence  to  be  derived  from  the  patient  himself  will  of  course 
vary  with  his  age,  as  pointed  out  in  the  section  on  Clinical  History. 
As  a  rule  little  or  no  difficulty  will  be  encountered  in  arriving  at  a 


DIAGNOSIS  399 

correct  diagnosis  of  a  case  of  congenital  syphilis  with  active  mani- 
festations at  birth.  The  skin  lesions,  the  snuffles,  the  hoarse  cry 
as  well  as  the  emaciated  condition  and  coffee  color  of  the  skin  will 
in  typical  cases  be  convincing.  Even  in  such  well-marked  cases 
a  Wassermann  test  should  be  made  as  corroborative  evidence  but 
more  as  a  guide  to  future  treatment. 

In  those  cases,  however,  in  which  no  symptoms  are  manifest  at 
birth  and  in  which  they  do  not  develop  in  a  typical  manner  the 
diagnosis  will  be  more  difficult. 

The  presence  of  enlarged  lymphatic  glands  can  be  relied  upon 
but  little  in  the  diagnosis  of  congenital  syphilis,  as  they  may  become 
enlarged  through  many  other  causes.  However,  the  absence  of 
such  enlargement  may  be  of  some  value,  as  one  or  more  of  the 
epitrochlear  glands  are  found  enlarged  in  the  early  course  of  the 
disease  in  from  80  to  90  per  cent,  of  cases  and  other  glands  quite 
frequently. 

Too  much  importance  should  not  be  placed  upon  the  so-called 
"snuffles,"  as  many  other  conditions  than  syphilis  may  cause  this 
symptom.  However,  taken  with  other  symptoms  of  syphilis  the 
snuffling  respiration  may  be  of  considerable  value.  The  finding 
of  treponemata  in  the  secretion  from  the  nose  would,  of  course,  be 
conclusive. 

Concerning  the  hoarse  cry  due  to  involvement  of  the  larynx,  prac- 
tically the  same  may  be  said.  Taken  alone  it  is  of  little  or  no  value, 
with  other  symptoms  it  may  be  considered  as  one  link  in  the  chain 
of  evidence. 

The  finding  of  iritis  in  early  infancy  or  childhood  should  at  once 
cause  the  physician  to  be  suspicious,  as  syphilis  is  the  most  frequent 
cause  of  this  condition  at  these  ages.  In  the  absence  of  other 
syphilitic  lesions,  however,  the  diagnosis  would  have  to  rest  on 
laboratory  findings. 

While  syphilis  is  by  far  the  most  frequent  cause  of  interstitial 
keratitis,  this  condition  should  not  be  considered  pathognomonic. 
Taken  with  other  evidence  of  congenital  syphilis,  much  reliance 
may  be  placed  on  it.  However,  the  diagnosis  should  be  confirmed 
by  laboratory  evidence. 

Rapidly  advancing  deafness  observed  between  the  fifteenth  and 
twentieth  years  without  otorrhea  or  earache,  should  be  looked  upon 
with  grave  suspicion  and  other  evidence  of  syphilis,  either  clinical 
or  laboratory,  be  searched  for  most  diligently. 

Hutchinson's  teeth  when  present  are  of  some  value  in  the  diag- 
nosis but  taken  alone  should  in  no  case  be  considered  as  conclusive. 
The  absence  of  this  condition  also  should  be  considered  as  far 
from  excluding  syphilis,  as  but  a  comparatively  small  percentage 
of  congenital  syphilitics  show  the  typical  Hutchinson's  teeth. 


400  DIAGNOSIS 

The  pseudoparalysis  occurring  in  early  congenital  syphilis  as 
a  result  of  involvement  of  the  long  bones  must  sometimes  be  dis- 
tinguished from  infantile  paralysis,  although  the  latter  condition 
is  rare  at  the  early  age,  the  former  condition  usually  is  observed. 
Other  manifestations  of  syphilis  nearly  always  are  present,  while 
the  a;-rays  will,  as  a  rule,  reveal  the  true  condition. 

The  so-called  Parrot's  nodes  and  craniotabes  are  of  a  certain 
value  in  the  diagnosis  of  congenital  syphilis,  but  in  the  absence  of 
other  manifestations  are  not  conclusive. 

LABORATORY   DIAGNOSIS. 

The  most  valuable  laboratory  procedure  in  congenital  syphilis 
is  the  Wassermann  reaction  on  the  blood  serum.  Methods  of 
collecting  blood  for  this  test  have  been  described  in  the  chapter 
on  Laboratory  Diagnosis  in  Part  I. 

Authorities  differ  as  to  the  value  of  the  Wassermann  test.  Holt^ 
states  that  it  is  positive  in  practically  100  per  cent,  of  untreated 
syphilitic  infants  and  even  in  those  who  have  received  mercury, 
unless  the  treatment  has  been  very  thorough  and  protracted. 
Veeder  and  Jeans^  found  92.6  per  cent,  of  82  cases  positive. 

No  accurate  statistics  are  available  concerning  the  Wassermann 
reaction  in  syphilis  hereditaria  tarde  but  it  is  stated  by  most  writers 
that  the  test  is  positive  in  practically  all  cases.  Coues's  case  of 
syphilitic  bursitis  mentioned  above  should  be  kept  in  mind  and  in 
doubtful  cases  therapeutic  tests  applied. 

The  luetin  test  is  also  of  distinct  value  in  congenital  syphilis. 
Noguchi^  states  that  it  is  positive  in  70  per  cent,  of  cases  and  that 
one  observer  found  it  positive  in  93  per  cent. 

Brown*  found  88  per  cent,  of  34  syphilitic  infants  gave  positive 
luetin  reactions  and  of  100  controls  96  gave  definitely  negative  tests 
and  4  were  doubtful. 

The  tests  on  the  spinal  fluid  are  the  same  as  those  employed  in 
the  spinal  fluid  of  patients  suffering  with  acquired  syphilis,  and  the 
results  are  the  same,  depending  upon  the  type  and  extent  of  the 
involvement  of  the  central  nervous  system. 

1  Am.  Jour.  Dis.  Child.,  1913,  vi,  p.  166. 

2  Ibid.,   1916,  xi,  p.   177. 

3  New  York  Med.  Jour.,  1914,  c,  p.  341. 

4  Am.  Jour.  Dis.  Child.,  1913,  vi,  p.  172. 


PLATE    V] 


Positive    Luetin    Reaction. 

Case  of  Congenital  Syphilis. 


CHAPTER    XXIV. 
PROGNOSIS,  PROPHYLAXIS  AND  TREATMENT. 

The  prognosis  of  congenital  syphilis  may  be  said  in  the  main 
to  be  bad,  although  this  statement  must  be  qualified  according  to 
the  age  of  the  patient  and  the  severity  of  the  lesions  and  symptoms. 
Infants  born  with  typical  active  manifestations  of  syphilis  almost 
invariably  succumb  to  the  disease,  while  those  in  whom  s\Tnptoms 
develop  only  after  a  few  days  to  a  few  weeks  stand  a  better  chance 
of  recovery  under  vigorous  specific  treatment.  It  has  been  stated 
that  in  the  comparatively  rare  cases  in  which  undoubted  marked 
clinical  symptoms  of  syphilis  exist  and  the  blood  gives  a  negative 
Wassermann  reaction,  the  prognosis  is  bad.  Congenital  syphilis 
developing  active  manifestations  at  puberty  or  later  must  also  be 
considered  of  grave  prognosis  although  some  cases  recover  under 
proper  therapy. 

Of  the  individual  symptoms  and  lesions  the  bullous  syphiloderm 
presents  one  of  the  most  unfavorable  prognoses.  If,  however,  it 
does  not  occur  for  some  time  after  birth  and  vigorous  treatment  is 
instituted  recovery  may  follow.  Involvement  of  the  viscera  in 
congenital  syphilis  renders  the  prognosis  most  unfavorable,  although 
as  pointed  out  above,  there  may  be  quite  marked  invasion  of  the 
heart  by  the  treponemata  without  clinical  manifestations.  Jaun- 
dice occiu-ring  in  congenital  syphilis,  according  to  Coutts,^  usually 
constitutes  an  unfavorable  prognosis,  as  most  cases  developing  this 
symptom  die. 

Of  the  eye  symptoms  interstitial  keratitis  usually  presents  a 
favorable  prognosis,  although  some  cases  are  most  refractory. 
The  prognosis  of  involvement  of  the  nervous  system  in  congenital 
syphilis  is  more  unfavorable  than  such  involvement  in  the  acquired 
form  of  the  disease,  and  most  cases  lead  on  to  a  fatal  termination. 
According  to  both  Mott^  and  Watson^  the  later  in  life  juvenile 
paresis  appears,  the  more  rapidly  fatal  will  be  its  course. 

Mortality. — The  following  table  given  by  Sturgis^  shows  the  num- 
ber of  births  and  deaths  of  syphilitic  children  in  the  Moscow 
Hospital  from  1860  to  1870. 

1  Cited  by  Still  in  Power  and  Murphy's  System  of  Syphilis,  London,  1909,  i,  p  360. 

2  Ibid.,  p.  361. 

3  Ibid. 

^  Morrow:  System  of   Genito-urinary   Diseases,    Syphilology   and   Dermatology, 
New  York,   1898,  ii,  p.  631. 
26 


402  PROGNOSIS,   PROPHYLAXIS  AND   TREATMENT 


Number  of 

Percent- 

Number   of 

Percen 

Years. 

children. 

Deaths. 

age. 

Years. 

children. 

Deaths. 

age. 

1860 

224 

148 

66 

1866 

165 

124 

70 

1861 

204 

150 

75 

1867 

174 

131 

69 

1862 

140      - 

93 

67 

1868 

208 

152 

73 

1863 

150 

123 

82 

1869 

184 

116 

63 

1864 

198 

139 

70 

1870 

184 

118 

65 

1865 

171 

131 

70 

It  will  be  seen  that  the  highest  percentage  of  deaths  was  82  in 
1863,  and  the  lowest  63  in  1869.  These  percentages,  however, 
must  be  too  high  and  undoubtedly  a  certain  number  of  congeni- 
tally  syphilitic  children  were  born  without  the  condition  being 
recognized. 

StilP  states  that  in  the  families  of  87  congenitally  syphilitic 
children  under  treatment,  there  were  39  stillbirths,  36  miscarriages, 
and  25  deaths  all  attributable  to  congenital  syphilis  while  of  the 
87  children  themselves,  13  died  while  under  observation. 

Post^  tabulated  the  mortality  in  30  syphilitic  famiHes  in  which 
there  had  been  168  pregnancies.  These  pregnancies  resulted  in 
53  stillbirths  and  miscarriages,  and  44  early  deaths,  a  total  of  97 
or  57  per  cent,  lost,  leaving  71  living  children,  of  which  32  have 
been  patients  and  39  presumably  healthy. 

PROPHYLAXIC. 

The  most  important  factor  in  the  prophylaxis  of  congenital 
syphilis  is  the  preventation  of  the  marriage  of  syphilitic  individuals. 
This  in  a  large  measure  could  be  accomplished  as  outlined  above 
by  the  requirement  of  a  clean  bill  of  health  in  regard  to  syphilis 
before  the  issuance  of  a  marriage  license.  If,  however,  syphilitics 
are  married,  the  prevention  of  conception  should  be  insisted  upon 
until  all  evidence  of  syphilis  is  absent,  that  is,  until  the  standard 
of  cure  proposed  in  Part  II  is  complied  with.  This  to  the  author's 
mind  applies  to  the  husband  as  well  as  to  the  wife,  for  he  believes 
that  a  man  may  be  infective  until  he  is  cured,  although  of  course 
the  chances  of  infection  are  much  less  when  active  manifestations 
are  not  present.  Finally,  if  conception  has  taken  place  when  either 
husband  or  wife  is  syphilitic  the  intensive  treatment  of  the  wife 
should  be  insisted  upon  even  if  she  shows  no  manifestations  of  the 
disease.  If  this  treatment  is  carried  on,  especially  the  adminis- 
tration of  salvarsan  throughout  the  course  of  pregnancy,  the  pre- 
vention of  congenital  syphilis  can  be  accomplished  in  the  vast 
majority  of  cases.  It  must  be  remembered,  however,  that  salvarsan 
should  be  administered  in  pregnancy  with  caution,  the  kidneys 
being  watched  most  carefully. 

1  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  i,  p,  359. 

2  Boston  Med.  and  Siffg.  Jour.,  1914,  clxx,  p.  113. 


TREATMENT  403 


TREATMENT. 


The  treatment  of  congenital  syphilis  is  in  the  main  the  same  as 
that  of  the  acquired  disease.  The  same  principles  are  involved 
and  the  same  methods  employed,  the  only  difference  lying  in  the 
manner  of  application  which  must  be  modified  to  suit  the  indiyidual 
needs. 

General  Treatment. —  Hygienic. — The  hygienic  treatment  of  con- 
genital syphilis  in  infants  consists  of  careful  nursing  with  cleanli- 
ness, the  frequent  change  of  diapers  and  the  free  use  of  powder, 
as  well  as  regularity  of  feeding  and  sleeping  and  plenty  of  fresh  air. 

Dietetic. — With  congenitally  syphilitic  infants  the  importance 
of  breast-feeding  is  not  to  be  overestimated.  If,  however,  the  child 
does  not  do  well  on  breast-feeding  the  milk  of  the  mother  should 
be  examined  and  if  found  unsuitable  a  syphilitic  wet-mirse  with 
suitable  milk  should  be  found  if  possible.  This,  however,  usually 
is  impossible,  when  modified  cow's  milk  must  be  substituted. 

The  hygienic  and  dietetic  treatment  of  older  children  and  of 
young  adults  with  congenital  syphilis  does  not  differ  materially 
from  that  of  acquired  syphilis. 

Specific  Treatment. — The  specific  treatment  of  congenital  syphilis 
consists  of  the  administration  of  mercury,  iodin  and  the  arsenical s, 
but  the  methods  of  administration  may  have  to  be  considerably 
modified. 

Mercury. — The  most  popular  methods  of  administering  mercury 
to  infants  are  by  the  mouth  and  by  the  application  to  the  body  of 
cloths  smeared  with  mercurial  ointment.  All  of  the  preparations 
of  mercury  administered  by  mouth  in  acquired  syphilis  have  been 
employed  in  congenital  syphilis.  The  gray  powder  in  doses  of 
0.03  to  0.06  gram  (^  to  1  grain)  three  times  a  day  is  very  satis- 
factory. This  may  be  deposited  on  the  child's  tongue  where  it  will 
readily  be  taken  up  or  it  may  be  administered  in  a  little  sweetened 
water  or  milk. 

In  administering  mercury  by  applying  the  ointment  to  the  skin 
a  cloth  of  suitable  size  is  smeared  with  4  to  S  grams  (1  to  2  drams) 
of  mercurial  ointment  or  with  a  like  amount  of  ointment  and 
vaseline  in  the  proportion  of  1  to  1  and  wound  around  the  child's 
body,  the  ointment  being  applied  to  the  back.  This  should  be 
removed  daily,  the  child  bathed  carefully  and  after  renewing  the 
ointment,  reapplied. 

^Mercurial  baths  have  been  employed  as  in  acquired  syphilis 
and  may  be  useful  in  certain  cases,  but  the  child  should  be  watched 
carefully  for  untoward  effects. 

The  intramuscular  injection  both  of  the  soluble  and  insoluble 
preparations  has  been  practised,  but  owing  to  the  pain  usually  is 


404  PROGNOSIS,   PROPHYLAXIS  AND   TREATMENT 

impractical  except  in  older  children  and  adults.  Certainly  the 
use  of  the  insoluble  preparations  has  nothing  to  recommend  it. 
The  intravenous  injection,  especially  of  mercurialized  serum,  is 
of  distinct  value  and  is  much  to  be  preferred  to  intramuscular 
injections. 

Salvarsan  and  Neosaharsan. — The  use  of  these  drugs  in  congen- 
ital syphilis  is  very  much  to  be  recommended  and  the  intravenous 
route  is  certainly  the  only  one  to  be  considered.  Quite  frequently, 
however,  intravenous  injections  in  infants  is  accomplished  with 
considerable  difficulty.  When  it  is  impossible  to  find  a  vein  at  the 
elbow  the  jugular  vein  may  be  employed,  or  better  still,  one  of 
the  veins  of  the  scalp  as  recommended  by  Holt  and  Brown. ^  The 
method  of  procedure  consists  of  securing  the  infant's  arms  in  a 
sheet  when  the  crying  of  the  child  and  the  hyperextention  of  the 
head  will  cause  the  veins  to  become  distended  and  prominent,  and 
either  the  posterior  auricular  or  one  of  the  branches  of  the  tem- 
poral may  be  employed. 

The  author  uses  the  apparatus  described  for  the  intravenous 
injection  of  mercury  and  neosalvarsan  (see  Fig.  54),  except  that 
two  5  c.c.  syringes  are  employed  instead  of  the  20  c.c.  ones. 

The  use  of  small  doses  is  to  be  recommended,  as  several  deaths 
have  occurred  in  infants  following  the  injection  of  salvarsan.  The 
same  dosage  should  be  employed  in  congenital  syphilis  as  in  the 
acquired  form,  that  is  0.006  gram  per  kilogram  of  body  weight. 
Thus,  an  infant  weighing  4  kilos  (8.8  pounds)  should  receive  0.024 
gram  of  salvarsan.  It  is  scarcely  necessary  to  state  that  the  same 
precautions  in  preparation  and  administration  should  be  employed 
in  congenital  syphilis  as  in  acquired  syphilis. 

lodin  in  any  form  is  rarely  employed  in  early  congenital  syphilis 
and  in  the  later  course  of  the  disease  should  be  administered  as  in 
acquired  syphilis. 

Symtomatic  and  Special  Treatment. — Only  such  conditions  as  are 
not  found  in  acquired  syphilis  or  require  treatment  differing  from 
similar  conditions  in  the  acquired  form  will  be  discussed  under 
this  head.  From  the  symptomatic  and  special  treatment  of  other 
conditions  the  chapter  on  Treatment  of  Acquired  Syphilis  should 
be  consulted. 

Skin  Lesions. — The  bullous  syphiloderm  usually  is  the  only  skin 
lesion  of  congenital  syphilis  which  needs  local  treatment.  The  blebs 
should  be  emptied  of  their  contents  and  if  the  epidermis  has  become 
detached  and  ulceration  exists,  the  lesions  should  be  dressed  with 
calomel  and  bismuth  powder  or  with  mercurial  ointment  diluted 
1  to  4  with  vaseline. 

1  Am.  Jour.  Dis.  Child.,  191.3,  vi,  p.  174. 


TREATMENT  405 

Mucous  Membranes. — As  infants  cannot  use  mouth  washes  or 
gargles  when  lesions  exist  in  the  mouth  it  should  be  swabbed  out 
with  potassium  chol orate  solution  several  times  a  day  or  the  lesions 
touched  with  a  5  to  10  per  cent,  silver  nitrate  solution. 

Rhinitis. — The  local  application  of  a  2  per  cent,  solution  of 
silver  nitrate  to  the  nostrils  will  assist  in  controlling  the  snuffles. 
Still^  recommends  the  use  of  adrenalin  solution  (1  to  1000)  in 
each  nostril  if  other  means  fail  to  give  relief.  If  ulceration  exists, 
the  nostrils  should  be  anointed  with  ammoniated  mercury  or  the 
yellow  oxide  of  mercury. 

The  Cure  of  Congenital  Syphilis. — The  same  standard  of  cure  of 
congenital  syphilis  is  required  as  in  acquired  syphilis,  although  it 
must  be  said  that  the  production  of  a  complete  clinical  and  biologi- 
cal cure  is  often  much  more  difficult  in  the  former  condition  than  in 
the  latter.  This  is  especially  true  of  syphilis  hereditaria  tarde. 
The  treatment,  however,  should  be  continued  at  least  periodically 
throughout  the  life  of  the  patient  as  long  as  any  evidence  of  active 
syphilis,  either  clinical  or  laboratory,  is  present. 

1  Power  and  Murphy:  System  of  Syphilis,  London,  1909,  i,  p.  364. 


INDEX. 


AcNEiFORM  syphiloderm,  84 
Acute  yellow  atrophy,  274 
Adenitis,  time  of  development  of,  67 
Adrenals,  syphilis  of,  28  i 
Age  and  syphilis,  43 
Aix-la-Chapelle,  189 
Alopecia,  complete,  case  of,  96 
syphilitic,  95 

clinical  history  of,  95 
diagnosis  of,  118 
differentiation    from  alopecia 
areata,  119 
from  premature  alopecia, 

119 
from  senile  alopecia,  119 
prognosis  of,  179 
treatment  of,  255 
Amboceptor,  preparation  of,  143 

preservation  of,  146 
Ancient  times,  syphilis  in,  17 
writings,  Chinese,  18 
Egyptian,  19 
Grecian,  19 
Hebrew,  19 
Hindoo,  19 
Japanese,  18 
Roman,  20 
Animal  inoculation,  34 
Anorexia  in  syphihs,  103 
Antigen,  137 

acetone  insoluble  lipoids,  139 
alcoholic  extracts,  138 
cholesterinized,  138 
Treponema  palUdum,  140 
Thompson's,  140 
Wassermann's  original,  137 
Aorta,  syphilis  of,  clinical  history  of, 
261 
diagnosis  of,  262 
pathology  of,  260 
prognosis  of,  262 
treatment  of,  262 
Appendages  of  skin,  syphilis  of,  95 
Arkansas  State  Hospital,  syphilis  in,  27 
Arsenic  in  treatment  of  syphilis,  211 
Arteries  of  brain,  syphilis  of,  clinical 
history  of,  322 
diagnosis  of,  335 


Arteries  of  brain,  syphilis  of,  pa'hology 
of,  314 
prognosis  of,  338 
of  spinal  cord,  syphilis  of,  clinical 
history  of,  328 
diagnosis  of,  335 
pathology  of,  323 
prognosis    f,  338 
and  veins,  syphilis  of,  260 
Arteritis  of  nervous  system,  differentia- 
tion from  arterio- 
sclerosis, 335 
from    chronic    alco- 

hoHsm,  336 
from  hysteria,  336 
from  multiple  sclero- 
sis, 336 
from,  paresis,  335 
from  uremic  poison- 
ing, 336 


Astruc,  Jean,  23 
Atoxyl,  212 


B 


Berlin,  syphilis  in,  26 
Bladder,  syphihs  of,  290 
Blood  picture  in  syphilis,  104 

prognosis  and,  180 
pressure  in  syphihs,  104 
of  syphilitics,  infectivity  of,  36 
Bones,  syphihs  of,  clinical  history  of, 
295 
diagnosis  of,  301 
differentiation      from      carci- 
noma, 301 
from  osteitis  deformans, 

301 
from  sarcoma,  301 
from  suppurative  osteo- 
myelitis, 301 
from  tuberculosis,  301 
pathology  of,  294 
prognosis  of,  302 
treatment  of,  302 
Brain    substance,   syphihs    of,   clinical 
history  of,  323 
diagnosis  of,  336 
pathology  of,  314 
prognosis  of,  339 


408 


INDEX 


Breast,  syphilis  of,  279 
British  Army,  syphihs  in,  27 
Bronchi,  syphihs  of,  264 
BuUous  syphiloderm,  dinical  history  of, 
83 
diagnosis  of,  115 
pathology  of,  53 
prognosis  of,  179 
Bursa?,  syphilis  of,  309 
Butyric  acid  test,  Noguchi's,  168 

Kaplan's  method,  169 
Thompson'  smodifi  cation, 
169 


Calomel  ointment  as  prophylactic,  184 
Cerebrospinal  fluid,  164 
anatomy  of,  164 
chemical  properties  of,  164 
complement-fixation  with,  175 
cytology  of,  174 
examination  of,  168 
proteins  in,  estimation  of,  168 
significance  of  increase  of, 
169 
physical  properties  of,  164 
physiology  of,  164 
reduction   of    Fehling's   solu- 
tion,   175 
Cervix,  syphilis  of,  285 
Chancre,  adenitis  following,  66 
of  anus,  61 
of  breast,  64 

differentiation      from      carci- 
noma, 110 
from  fissure,  110 
from  gumma,  110 
of  cervix,  60 

differentiation    from    epithe- 
lioma,  109 
clinical  history  of,  68 
complications  of,  65 
development  of,  58 
eroded,  65 

extragenital,  clinical  history  of,  61 
diagnosis  of,  109 
prognosis  of,  178 
prophylaxis  of,  185 
treatment  of,  253 
of  eyelid,  64 

diagnosis  of,  110 
of  finger,  64 

diagnosis  of.  111 
genital,  59 

diagnosis  of,  108 
differentiation    from    chancre 
redux,  109 
from  chancroid,  108 
from  herpes,  109 
from  scabies,  109 


Chancre,  genital,   differentiation  from 
simple  erosion,  108 
of  glans  penis,  59 
of  groin,  61 
histopathology  of,  47 
Hunterian,  65 
of  labia  majora,  60 
labial,  62 

differentiation    from     epithe- 
lioma, 109 
lingual,  64 

differentiation     from     simple 
ulcer,  110 
from  tubercular  ulcer,  110 
location  of,  59 
of  preputial  orifice,  59 
of  prescrotal  angle,  60 
prognosis  of,  177 
of  rectum,  61 
redux,  65,  103 
of  scrotum,  60 
of  skin  of  penis,  59 
of  tonsil,  62 

differentiation   from    abscess, 
110 
from  cancer,  110 
from  diphtheria,  110 
from  gumma,  110 
from  simple  angina,  110 
from    Vincent's    angina, 
110 
treatment  of,  252 
ulcerating,  65 
of  urethra,  60 

differentiation     from     gonor- 
rhea, 109 
of  urinary  meatus,  59 
of  vagina,  60 
varieties  of,  65 
Charcot's  joint,  305,  307,  308 
Cholesterinized  antigens,  138 
Choroid,  syphilis  of,  clinical  history  of, 
359 
diagnosis  of,  361 
pathology  of,  357 
prognosis  of,  363 
treatment  of,  364 
Ciliary  body,  syphilis  of,  clinical  history 
of,  358 
diagnosis  of,  361 
pathology  of,  356 
prognosis  of,  362 
Cincinnati  City  Hospital,  deaths  from 

syphilis  in,  28 
Circulatory  system,  syphilis  of,  257 
Circumcision    as    a    prophylactic    of 

syphilis,  185 
Cirrhosis,  syphilitic,  274 
Civil  state  and  syphihs,  45 
Civilization  and  syphilis,  45 
Climate  and  syphilis,  45 
Cobra  venom  test  of  Weil,  159 


INDEX 


409 


Collargol    in    demonstrating    trepone- 

mata,  126 
CoUes'  law,  42 
Colloidal  gold  test,  169 

preparation    of    reagent, 

170 
technic  of,  171 
value  of,  173 
Complement,  collection  of,  141 

preservation  of,  142 
Comi)lcment-fixation  tests,  130 

Noguchi's  method,  147 

preparation  of  reagents,  134 

principles  of,  130 

technic  of,  134 

theory  of,  154 

Thompson's  method,  149 

value  of,  155 

Wassermann's  method  of,  146 
Condyloma.     {See  Vegetating  Syphilo- 

derm.) 
Congenital  syphUis,  367 

adrenals  in,  387 

alopecia  in,  379 

arteries  in,  382 

blood  in,  379 

bones  in,  388 

bronchi  in,  383 

bullous  syphiloderm  in,  376 

bursse  in,  390 

clinical  history  of,  372 

diagnosis  of,  398 
laboratory,  400 

ear  in,  397 

esophagus  in,  384 

etiology  of,  368 

eye  in,  396 

gall-bladder  in,  386 

gastro-mtestinal  tract  in,  383 

genito-urinary  organs  in,  387 

gummatous    sj^philoderm    in, 
378 

heart  in,  381 

historical,  367 

intestines  in,  384 

joints  in,  390 

kidneys  in,  387 

larynx  in,  382 

late  development  of,  373 

liver  in,  385 

lungs  in,  383 

lymphatic  glands  in,  374 

macular  syphiloderm  in,  374 

maculopapular      syphiloderm 
in,  375 

mortality  in,  401 

mouth  in,  383 

mucous  membranes  in,  379 

muscles  in,  391 

in  negroes,  370 

nervous  system  in,  392 

nodular  syphiloderm  in,  375 


Congenital  syphilis,   nomenclature  of, 
367 

onychia  in,  379 

ovaries  in,  387 

pancreas  in,  386 

papular  syphiloderm  in,  375 

paresis  in,  393 

paronychia  in,  379 

pathology  of,  372 

prognosis  of,  401 

pro])hylaxis  of,  402 

pulse  in,  379 

pustular  syphiloderm  in,  376 

respiratory  tract  in,  382 

rhinitis  in,  382 

scaphoid  scapula  in,  390 

secondary   etiological   factors 
of,  370 

snuffles  in,  382 

spleen  in,  386 

stomach  in,  384 

symptoms  in,  379 

syphilodermata  in,  374 

tabes  dorsalis  in,  396 

teeth  in,  383 

temperature  in,  379 

tendons  in,  391 

testicles  in,  387 

thymus  in,  386 

thyroid  in,  386 

trachea  in,  383 

treatment  of,  403 

uterus  in,  387 

veins  in,  382 

vesicular  syphiloderm  in,  375 
Cornea,  syphilis  of,  clinical  history  of, 
359 

diagnosis  of,  361 

pathology  of,  356 

prognosis  of,  362 

treatment  of,  363 
Corpuscle  suspension,  146 
Coryza  iodica,  250 
Craniotabes,  389 
Cytoryctes  luis,  32 


Dactylitis,  300 
Dark-field  illumination,  123 
Development  and  course  of  syphilis,  56 
Direct  contact,  infection  by,  40 
Disse  and  Taguchi,  diplococcus  of,  32 
Drinking  cups,  infection  by,  41 


Ear,  syphilis  of,  364 

clinical  history,  365 
diagnosis  of,  365 


410 


INDEX 


Ear,  syphilis  of,  pathology  of,  364 

prognosis  of,  366 

treatment  of,  366 
Economic  importance  of  syphilis,  27 
Endocarditis,  syphilitic,  258 
Enzyme  test,  160 
Esophagus,  syphUis  of,  289 
Etiology,  30 

early  views,  30 
microbiology,  31 
Extragenital  chancre,  61 
Eye,  syphilis  of,  356 

clinical  history  of,  358 

diagnosis  of,  361 

pathology  of,  356 

prognosis  of,  362 

treatment  of,  363 


Fallopian  tubes,  syphilis  of,  288 

FaUopio,  Gabrille,  23 

Fernal,  John,  23 

Folhcular  syphiloderm,  73 

Fowler's  solution,  212 

Fracastoro,  22 

Frankel  treatment  of  tabes,  354 


G 


Gall-bladder,  syphilis  of,  277 
Gastritis,  syphilitic,  271 
Gastro-intestinal  tract,  syphilis  of,  268 
Genito-urinary  organs,  syphilis  of,  282 
Geographical  distribution  of  syphilis,  25 
Giemsa's  stain  for  treponemata,  126 
Goldhorn's  stain  for  treponemata,  127 
Gray  powder,  195 
Gummata  of  bone,  294 

of  brain  substance,  clinical  history 
of,  323 
diagnosis  of,  336 
pathology  of,  314 
prognosis  of,  338 
surgery  of,  353 
of  ciliary  body,  358 
of  cornea,  359 
of  iris,  358 
of  liver,  274 

differentiation      from      carci- 
noma, 276 
of  meninges,  313-321 
of  spinal  cord,  clinical  history  of, 
328 
diagnosis  of,  337 
pathology  of,  315 
prognosis  of,  339 
treatment  of,  353 
of  stomach,  271 


Gummatous  syphiloderm,  clinical  his- 
tory of,  92 
diagnosis  of,  117 
differentiation   from    abscess, 
117 
from  chancre,  109 
from  chancroid,  117 
from  epithelioma,  118 
from  fibroid,  117 
from  lipoma,  117 
from  lupus,  118 
from  sarcoma,  117 
from  varicose  ulcer,  118 
histopathology  of,  53 
syphilomycoderm,  clinical  history 
of,  103 
diagnosis  of,  120 


H 


"Hair  cut,"  58 

syphilis  of,  95 
Heart,  syphilis  of,  257 
Hecht- Weinberg  reaction,  158 
Herxheimer  reaction,  237 
Hoffmann,   cultivation  of  Treponema 

pallidum  by,  38 
Hot  springs  of  Arkansas,  189 
Hunter,  John,  23 
Hutchinson  teeth,  384 
Hydrocephalus,  392 
Hypophysis,  syphilis  of,  281 


Icterus  in  syphilis,  274 

Idiosyncrasy,  42 

Immunity  in  syphilis,  42 

India-ink    method    of     demonstrating 

treponemata,  126 
Indurated  papule,  65 
Intermediate  contact,  infection  by,  41 
Intracranial  therapy,  results  of,  350 

technic  of,  344 
Intraspinal  therapy,  341 

rational,  345 

results  of,  349 

technic  of,  344 

untoward  effects  of,  350 
Intraventricular  therapy,  results  of,  350 

technic  of,  345 
lodid  acne,  250 
lodin  in  syphilis,  246 

administration  of,  247 

elimination  of,  251 

therapeutic  effects  of,  249 

untoward  effects  of,  250 
lodipin,  248 
lodism,  250 
Iodoform,  248 


INDEX 


411 


lothion,  248 

Iris,  syphilis  of,  clinical  history  of,  358 

diagnosis  of,  361 

pathology  of,  356 

prognosis  of,  362 

treatment  of,  363 


Jarisch-Herxheimer  reaction,  237 
Jenner's  stain  for  treponemata,  127 
Joint,  Charcot's,  305,  307,  308 
Joints,  syphilis  of,  clinical  history  of, 
305 
diagnosis  of,  307 
differentiation  from  acute  arti- 
cular rheumatism,  307 
from  gonorrheal  arthritis, 

307 
from  rheumatoid  arthri- 
tis, 308 
from  tuberculosis,  308 
pathology  of,  303 
prognosis  of,  308 
treatment  of,  308 
Joseph  and  Piorkowsky,  bacillus  of,  32 
Juvenile  paresis,  393 
tabes,  396 


K 


Keidel  tube,  135 

Kidney,  syphilis  of,  clinical  history  of, 
291 

diagnosis  of,  292 

pathology  of,  291 

prognosis  of,  293 

treatment  of,  293 


Labial  chancre,  62 
Laboratory  diagnosis,  122 
Lacrimal  apparatus,  syphilis  of,  clini- 
cal history  of,  361 
diagnosis  of,  362 
pathology  of,  358 
prognosis  of,  363 
treatment  of,  364 
Landau's  color  test,  160 
Lange  colloidal  gold  test,  169 
Larynx,  syphilis  of,  263 
Leukocytes  in  syphilis,  105 
Leukocytozoon  syphilidis,  33 
Leukoplakia,  chnical  liistory  of,  102 
diagnosis  of,  120 

differentiation  from  psoriasis,  120 
prognosis  of,  180 
Lingual  chancre,  64 
Liver,  syphilis  of,  clinical  history  of,  274 


Liver,  syphilis  of,  diagnosis  of,  276 
pathology  of,  274 
prognosis  of,  276 
treatment  of,  277 
Los  Angeles  County  Hospital,  deaths 
following  intraspinal  therapy  in,  351 
Luetin,  160 

experimentation,  161 
preparation  of,  160 
technic  of  injection  of,  161 
tjqaes  of  reaction  of,  161 
value  of,  163 
Lumbar  puncture.   {See  Rachicentesis.) 
Lungs,  syphilis  of,  265 

clinical  history  of,  266 
diagnosis  of,  267 
pathology  of,  265 
prognosis  of,  267 
treatment  of,  267 
Lustgarten's  bacillus,  31 
Lymphatic  glands,  syphilis  of,  clinical 
history  of,  66 
diagnosis  of,  111 
diagnostic  importance  of, 

111 
gummata  of,  68 
pathology  of,  48 
prognosis  of.  178 
treatment  of,  253 


M 


McDonagh's  leukocytozoon  s>Tphilidis, 

33 
Macular  syphiloderm,  annular,  clinical 
history  of,  69 
diagnosis  of,  113 
histopathology  of,  50 
pigmentary,    clinical    history 
of,  69 
differentiation  from  chlo- 
asma, 113 
from  tinea  versicolar, 

113 
from  vitiligo,  113 
roseolar,  clinical  history  of,  68 
diagnosis  of,  112 
differentiation  from  drug 
rashes,  113 
from         German 

measles,  113 
from  measles,  113 
from  tinea  versicolar, 
113 
syphilomycoderm,  clinical  history 
of,  100 
diagnosis  of,  119 
differentiation  from  aphthous 
sore,  120 
from  diphtheria,  120 
from  herpes,  120 


412 


INDEX 


Macular    syphilomj^coderm,    differen- 
tiation from  mercurial  ulcer,  120 
Maculopapular  sjqDhiloderm,  72 
Malaise  in  S5^philis,  103 
Marriage  of  sj'philitics,  180 
Medieval  times,  SA'philis  in,  20 
Meniere's  sj'^ndrome,  365 
Meninges,  sj^ihilis  of,  clinical  history 
of,  317 
diagnosis  of,  335 
differentiation  from  non-speci- 
fic meningitis,  335 
pathology  of,  313 
Mercury,  contraindications  to,  206 
effects  on  Wassermann,  241 
fumigation,  198 
history  of  use  of,  194 
injections,  intramuscular,  198 

comparative  value  of  var- 
ious   preparations    of, 
202 
insoluble  preparations  of, 

199 
soluble    preparations    of, 

200 
technic  of,  201 
intravenous,  204 

Nixon's  method  of,  205 
inunctions  of,  196 
mouth  administration  of,  194 
phj'siological  action  of,  207 
plasters  of,  197 

precautions  in  administermg,  206 
suppositories  of,  205 
untoward  effects  of,  208 
value  of,  compared  with  salvarsan, 
240 
Metchnikoff,  24 
Mixed  sore,  65 

treatment,  252 
Modes  of  transmission  of  syphilis,  40 
Mortality  of  syphilis,  182 
Mouth,  s3T3hihs  of,  268 
Mucous    membranes.      {See    Syphilo- 
mycodermata.) 
patch.      (See     Papular      Erosive 
Sj'^philomycoderm.) 
Mullens,  cultivation  of  Treponema  pal- 

hdum  by,  38 
JNIuscles,  syphilLs  of,  310 
Myelitis,  syphilitic,  clinical  historj^  of, 
328 
diagnosis  of,  337 
prognosis  of,  339 
Myocarditis,  syphilitic,  258 


N 


Ntuls.    (See  On3'chia  and  Paronj^chia.) 
Naples,  epidemic  of,  22 
Neisser's  paste,  185 


Neosalvarsan,  222 

Nerves,  syphilis  of,  clinical  history  of, 
334 
diagnosis  of,  338 
pathology  of,  317 
prognosis  of,  340 
treatment  of,  354 
Nervous  system,  syphilis  of,  312 

clinical  history  of,  317 

diagnosis  of,  335 

early     involvement     of, 

317 
history  of,  312 
mortality  of,  340 
pathology  of,  312 
prognosis  of,  338 
treatment    of,  •  standard, 
354 
symptomatic,   353 
Neuralgia,  syphilitic,  335 
Neuritis,  syphihtic,  335 
New  World  origin  of  syphilis,  21 
New  York  City,  syphilis  in,  26 
Nodular  syphiloderm,   clinical  history 
of,  90 
diagnosis  of,  116 
differentiation      from       acne 
rosacea,  117 
from  epithelioma,  116 
from  leprosy,  117 
histopathology  of,  53 
Noguchi's  method  of  cultivating  Tre- 
ponema pallidum,  38 
Nomenclature,  22 
Nonne-Apelt  test,  168 
Nummular  syphiloderm,  75 


Occupation  and  syphilis,  45 
Ogilvie  treatment,  results  of,  349 

technic  of,  343 
Old  World,  syphilis  in,  17 
Onychia,  clinical  history  of,  98 
diagnosis  of,  119 
differentiation  from  eczema,  119 

from  psoriasis,  119 
prognosis  of,  179 
treatment  of,  255 
Optic  nerve,  syphilis  of,  clinical  history 
of,  360 
diagnosis  of,  362 
pathology  of,  357 
prognosis  of,  363 
treatment  of,  364 
Orbit,  syphilis    of,  clinical   history  of, 
361 
diagnosis  of,  362 
pathology  of,  358 
prognosis  of,  363 
Ovaries,  syphilis  of,  288 


INDEX 


413 


Palmar  syphiloderm,   clinical  history 
of,  79 
diagnosis  of,  115 
differentiation  from  dermatitis 
seborrheica,  115 
from   squamous   eczema, 
115 
Pancreas,  syphilis  of,  278 
Papular  syphiloderm,  annular,  clinical 
history  of,  76 
differentiation  from  ery- 
thema multiforme, 
114 
from  psoriasis,  114 
from  tinea  circinata, 
114 
histopathology  of,  51 
clinical  history  of,  72 
histopathology  of,  50 
lenticular,  clinical  history  of, 
74 
diagnosis  of,  114 
miliary,  clinical  history  of,  73 
diagnosis  of,  113 
differentiation  from  acne, 
114 
from  keratosis  pila- 
ris, 113 
from   lichen  planus, 
113 
scrofulosis,  113 
from  papular  eczema, 

114 
from  pityriasis  rubra 

pilaris,  114 
from  psoriasis,  113 
from  scabies,  113 
moist,  clinical  history  of,  80 
differentiation  from  ver- 

uca  acuminata,  115 
histopathology  of,  51 
syphilomycoderm,  clinical  history 
of,  101 
diagnosis  of,  120 
Papulosquamous  syphiloderm,  clinical 
history  of,  78 
diagnosis  of,  114 
differentiation  from  psoriasis, 
114 
Parental  infection,  369 
Paresis,  chnical  history  of,  323 
diagnosis  of,  336 
mortahty  of,  339 
pathology  of,  315 
prognosis  of,  339 
symptoms  of,  bladder,  328 
mental,  323 
neurological,  325 
Paretic  brain  substance,  infectivity  of, 
36 


Paretic  convulsions,  326 

treatment  of,  353 
Paris,  syphilis  in,  26 
Paronychia,  179 

clinical  history  of,  99 
diagnosis  of,  119 
treatment  of,  255 
Parrot's  nodes,  389 
Penis,  gummata  of,  282 
Perforating  ulcer,  334 
Pericarditis,  syphilitic,  258 
Perigenital  chancres,  61 
PharjTix,  syphiUs  of,  268 
Pituitary  body,  syphilis  of,  281 
Placenta,  syphilis  of,  372 
Plantar  syphUoderm,  clinical  history  of, 
79 
diagnosis  of,  115 
Pleocytosis,  significance  of,  175 
Pleurse,  sj^ihilis  of,  267 
Polydipsia  in  sj'philis,  104 
Potassium  iodide  in  syphilis,  246 

methods  of  administering, 
247 
Precipitin  tests,  159 
Prehistoric  times,  syphilis  in,  17 
Prevalence  of  syphilis,  25 
Primary  stage  of  Ricord,  55 
Prophylaxis,  184 

and  education,  186 
and  legislation,  187 
personal  measures,  184 
pubUc  measm-es,  185 
Prostate,  syphilis  of,  284 
Prostitution,  regulation  of,  185 
Provocative  Wassermann  test,  157 
Pulse  in  syphilis,  104 
Pustular  syphiloderm,  accuminate, 
clinical  history  of,  84 
diagnosis  of,  115 
histopathology^  of,  53 
large  flat,  clinical  history  of,  86 
diagnosis  of,  116 
histopathology^  of,  53 
small  flat,  clinical  history  of, 
85 
diagnosis  of,  116 
histopathology  of,  53 
Pustulocrustaceous  syphiloderm,  87 


Quaternary  stage  of  Foiu-nier,  55 


R 


Rabbits,  inoculation  of,  with  s"\'philis, 

35 
Race  and  syphilis,  44 
Rachicentesis,  contraindications  of,  165 


414 


INDEX 


Rachicentesis,  indications  of,  165 
technic  of,  165 
untoward  effects  of,  168 
Ravaut  treatment,  results  of,  349 

technic  of,  342 
Recurring  or  relapsing  chancre,  65 
Registration  area,  deaths  from  syphilis 

in,  28 
Respiration  in  syphUis,  104 
Respiratory  tract,  syphilis  of,  263 
Retina,  syphilis  of,  clinical '  history  of, 
360 
diagnosis  of,  362 
pathology  of,  357 
prognosis  of,  363 
treatment  of,  364 
Ricord,  Phillippe,  23 
Ricord's  classification  inadequate,  55 
Rupia,  clinical  history  of,  88 
diagnosis  of,  116 
histopathology  of,  53 


Salvarsan,  215 
action  of,  232 
after-care  of  patient,  232 
chemical  properties  of,  217 
contraindications  for,  231 
dosage  of,  224 

effect  of,  on  Wassermann,  244 
enteroclysis,  222 
fatalities  from,  238 
fate  of,  in  body,  239 
history,  of,  215 
indications  for,  230 
intramuscularly,  219 
intravenously,  220 
natrium,  223 
oily  preparations  of,  220 
physical  properties  of,  217 
preparation  of  patient  for,  232 
reactions  following,  235 

significance  of,  236 
subcutaneously,  219 
technic  of  injections  of,  224 
untoward  effects  of,  232 
value  of,  compared  with  mercury, 
240 
Scaphoid  scapula,  390 
Schereschewsky,  cultivation  of  Trepo- 
nema pallidum  by,  37 
Sclera,  syphilis  of,  clinical  history  of, 
359 
diagnosis  of,  361 
pathology  of,  356 
prognosis  of,  363 
treatment  of,  364 
Secondary  etiological  factors,  42 

stage  of  Ricord,  55 
Seminal  vesicles,  syphilis  of,  285 
Serpiginous  nodular  syphiloderm,  91 


Serum,    methods    of    obtaining    from 

patients,  134 
Sex  and  syphilis,  43 
Siegel's  cytoryctes  luis,  32 
"Snuffles"  in  congenital  syphilis,  382 
Soamin,  213 

Social  condition  and  syphilis,  45 
Sodium  cacodylate,  213 

effect  on  Wassermann,  246 
Spinal  cord,  gummata  of,  337 

syphilis  of,  clinical  history, 
328 
diagnosis  of,  337 
pathology  of,  315 
prognosis  of,  339 
fluid.     {See  Cerebrospinal  Fluid.) 
puncture.     {See  Rachicentesis.) 
Spleen,  syphihs  of,  277 
Squamous  papular  syphiloderm,  51 
Stomach  and  intestines,  syphilis  of,  270 
Subconjunctival  injections  of  salvarsan- 

ized  serum,  364 
Sucking,  infection  by,  41 
Swift-Elhs  treatment,  342 
Synechia  following  iritis,  356 
Syphilodermata,  classification  of,  49 
diagnosis  of,  112 
histopathology  of,  49 
prognosis  of,  178 
treatment  of,  254 
Syphilomycodermata,  classification  of, 
54 
clinical  history  of,  100 
diagnosis  of,  119 
histopathology  of,  54 
prognosis  of,  180 
treatment  of,  255 
Syphilis  and  marriage,  180 
hereditaria  tarde,  369 
modes  of  transmission  of,  40 
Syphilitic  fever,  104 

and  prognosis,  180 
psoriasis,  78 


Tabes  dorsalis,  anesthesia  in,  330 

Argyll-Robertson  pupil  in,  332 
ataxia  in,  331 
bones  in,  334 
clinical  history  of,  329 
clitoris  crises  in,  333 
decubitus  in,  334 
diagnosis  of,  337 
genital  organs  in,  333 
intestinal  crises  in,  333 
involuntary    movements    in, 

332 
laryngeal  crises  in,  334 
muscles  in,  334 
nephritic  crises  in,  333 
paralysis  in,  332 


INDEX 


415 


Tabes  dorsalis,  pathology  of,  317 
perforating  ulcer  in,  334 
prognosis  of,  340 
sexual  appetite  in,  333 
symptoms  of,  auditory ,  332 
bladder,  333 
motor,  330 
reflex,  332 
sensory,  329 
trophic,  334 
visual,  332 
treatment    of,    symptomatic, 
354 
and     paresis,     less     frequent     in 
females,  44 
Taboparesis,  cUnical  history  of,  334 
diagnosis  of,  338 
pathology  of,  317 
prognosis  of,  340 
Temperature  in  syphilis,  104 
Tendons,  syphilis  of,  309 
Tertiary  stage  of  Ricord,  55 
Testicle,  syphilis  of,  282  _ 
Third  generation,  syphilis  in,  371 
Thymus,  syphilis  of,  280 
Thyroid,  syphilis  of,  280 
Tiodine,  248 
Toilets,  infection  by,  41 
Towels,  infection  by,  41 
Trachea,  syphilis  of,  264 
Treatment  of  syphilis,  188 
diatetic,  189 
hydrotherapeutic,  189 
hygienic,  188 
specific,  194 

symptomatic  and  special,  252 
tonic,  194 
Treponema  palhdum,  agglutination  of, 
37 
biology  of,  33 
collection  of  material,  122 
cultivation  of,  37 

Noguchi's  method,  38 
Zinnser's  method,  40 
demonstration  of,  122 
different  strains  of,  37 
discovery  of,  32 
identification  of,  in  pure  cul- 
ture, 40 
length  of  life  on  towels  and 

glass,  41 
location  of,  34 
morphology  of,  33 
in     paretic     brains,    staining 
method,  129 


Treponema  pallidum,  staining  of  smears 
of,  126 
in  tissue,  127 
Tuiiercular  sj^philoderm.     {See  Nodu- 
lar Syphiloderm.) 
Tuberculopustular  syphiloderm,  91 
Tuberculosquamous  syphiloderm,  91 


Umbilical  cord,  syphiUs  of,  372 

United  States  Army,  syphilis  in,  27 
deaths  from  syphilis  in,  28 
syphilis  in,  Banks'  estimation 
of,  26 

Ureter,  syphilis  of,  290 

Urethra,  syphilis  of,  289 

Urethral  chancre,  60 

Uterus,  syphilis  of,  287 


Vagina,  syphilis  of,  285 
Vaginal  chancre,  60 
Varioliform  syphiloderm,  84 
Vegetating  syphiloderm,  clinical  history 
of,  82 
histopathology  of,  51 
syphilomycoderm,  102 
Venarsen,  214 

Vesicular  syphiloderm,  clinical  history 
of,  82 
diagnosis  of,  115 
histopathology  of,  52 


W 


Wassermann    test    in    diseases    other 
than  syphilis,  157 

and  prognosis,  177 

provocative,  157 

technic  of,  146 
West  Point  cadets,  syphilis  among,  27 
Wile  treatment,  results  of,  349 

technic  of.  344 


ZiNNSER,  Hopkins  and  Gilbert,  method 
of  cultivating  treponemata,  40 


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